A deadly gut infection may come down to a sugar in ice cream(arstechnica.com)
arstechnica.com
A deadly gut infection may come down to a sugar in ice cream
https://arstechnica.com/science/2018/01/the-curious-case-of-a-boring-sugar-that-may-have-unleashed-a-savage-plague/
65 comments
Don't overlook that first paragraph, fluoroquinolones are some of the most dangerous antibiotics available, but prescribed for common infections (which they shouldn't be). Fluoroquinolones kill most human gut bacteria (irreversibly) except c.diff, leading to overgrowth.
I got prescribed Ciproflaxin once, a fluoroquinolone, and was just told it was an antibiotic, not warned about any potential side effects from the doctor, just acted like it was just like every other antibiotic I ever took, and I was to take it for 30 days straight.
I thought it was weird when the information page that came with the pills said "do not exercise while taking this medication and for at least a month afterwards", as well as a long list of side effects.
I took the first dose, and the very next day I started feeling tingly neuropathy in my extremities. I kept taking the medication for a few days while being worried about it, and it started spreading to other parts of my body. I started reading anecdotes online about how Cipro destroyed people's bodies, snapped tendons (especially the achilles tendon, one of the weaker tendons apparently, hence the don't exercise warning), and has side effects that last for years afterwards and getting even more paranoid about it.
Day 7 I start feeling the tingling in my face, and that prompted me to call the doctor. They got me on a non-fluroquinolone for the rest of the 30 days.
I have had periods of neuropathy on and off for years after that, including in my face, for the past four years since. It seems to have become less frequent recently though, finally. Mind you, this is after taking only 7 pills total four years ago.
It's so dangerous, and pretty much every doctor I've told this too since have been surprised that it could cause such problems.
FDA had to issue a warning (unfortunately after I was prescribed), telling doctors not to prescribe it for minor infections, and saying it had potentially permanent serious side effects, involving tendons, muscles, joints, nerves, and central nervous system: https://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
I thought it was weird when the information page that came with the pills said "do not exercise while taking this medication and for at least a month afterwards", as well as a long list of side effects.
I took the first dose, and the very next day I started feeling tingly neuropathy in my extremities. I kept taking the medication for a few days while being worried about it, and it started spreading to other parts of my body. I started reading anecdotes online about how Cipro destroyed people's bodies, snapped tendons (especially the achilles tendon, one of the weaker tendons apparently, hence the don't exercise warning), and has side effects that last for years afterwards and getting even more paranoid about it.
Day 7 I start feeling the tingling in my face, and that prompted me to call the doctor. They got me on a non-fluroquinolone for the rest of the 30 days.
I have had periods of neuropathy on and off for years after that, including in my face, for the past four years since. It seems to have become less frequent recently though, finally. Mind you, this is after taking only 7 pills total four years ago.
It's so dangerous, and pretty much every doctor I've told this too since have been surprised that it could cause such problems.
FDA had to issue a warning (unfortunately after I was prescribed), telling doctors not to prescribe it for minor infections, and saying it had potentially permanent serious side effects, involving tendons, muscles, joints, nerves, and central nervous system: https://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
That's fucking terrifying. I am really sorry to hear that...I'm sure it has frustrated you to no end that something so minor, prescribed by a doctor no less, has caused such a long-lasting impact. It's great that the neuropathy has become less and less frequent. Here's hoping that trend continues. Thank you for sharing the information.
I'm sorry to hear that, I too have permanent nerve damage from a short course of fluoroquinolones. I'm assuming none of your doctors had any clue it was related, what was going on, or how to help you?
I had almost the same exact experience after just three days taking the medication. Dizziness, passing out, burning and tingling of extremities. I’m still really freaked out by the experience.
PLEASE make sure you know the risks before taking ciproflaxin.
PLEASE make sure you know the risks before taking ciproflaxin.
I can't tell if it's your intention, but your phrasing blames patients for taking drugs prescribed by doctors. We need the medical community to understand this and stop prescribing. Fluoroquinolones have misleading and false safety profiles that make it hard for a patient to truly evaluate the risk. Doctors need to understand how these drugs work, because if they did, they wouldn't prescribe them.
Should doctors ever prescribe antibiotics for minor infections unless the patient is in some kind of high-risk group?
As someone who was on Cipro for... I think just shy of two years, I feel like I dodged a bullet.
Fluoroquinolones are molecularly designed to destroy most cells in the human body, so it's unclear why some people are affected more than others. Two things to consider: Fluoroquinolone side effects can be so outrageous that people don't know to look for them or link them to antibiotics. For example, sensitivity to light, increased anxiety or depression, unexplained tendinopathy or random stabbing pains around the body, weakness or instability in joints, unexplained dizziness, heart palpitations, are some of the dozens of possible "milder" symptoms. Secondly, the delayed toxicity of fluoroquinolone antibiotics can cause permanent damage years after stopping the drug. Anecdotally a story just surfaced of a woman with a spontaneous tendon rupture 7 years after stopping cipro. Something like permanent mitochondrial damage, or delayed genetic damage, or delayed oxidative stress, which fluoroquinolones are well documented to cause, may weaken the body slowly over time.
A missing piece of information is that trehalose is a rather new additive. It was very expensive to manufacture until about 20 years ago when a new cheaper process to make it was found. And voilà, because it appears safe and is somewhat useful, it starts showing up in all sorts of products without any labeling indication. And the fallout is just now being noticed. One of the commenters used the phrase "food science" ... hah! We're the guinea pigs!
Not missing. In paragraphs 5 and 6, the article explains how, just before c. diff infections started to get more common, a new method for producing it that dropped the price by over 99% was developed.
I wonder if Japan had higher c.diff rates before global use since trehalose was common there first.
> With tinkering, syrup scientists at Japan’s Hayashibara chemistry company finally figured out a novel enzymatic method to make it on the cheap from starch. The method brought costs down to just $3 per kilogram. By 2000—just before the rise of C. diff.—the company got approval from the US Food and Drug Administration to use it as an additive in food. Approval for use in Europe came the following year. Manufacturers started pouring trehalose into a variety of foods, from pasta to ground beef to ice creams.
We really are the guinea pigs. The supplement and sports nutrition industry can essentially mix whatever sounds good for marketing and throw it over the wall.
Thank Orrin Hatch.
I notice they had to add the bacteria to the mice to do the test. I wonder if some of the instances when drugs work on mice but not in human trials are due to the different gut bacteria at work?
There are any number of reasons why drugs don't work on humans when they do work on other animals. It could be gut bacteria, but it could just be that the animal has some other physiological trait that causes the drug to be more or less effective.
In this case, they weren't testing a drug, they were testing the deadliness of the bacteria. It doesn't matter _how_ toxic the bacteria is to humans relative to mice, it only matters that the bacteria is more deadly (or less deadly) to the mice when the sugar is present.
In this case, they weren't testing a drug, they were testing the deadliness of the bacteria. It doesn't matter _how_ toxic the bacteria is to humans relative to mice, it only matters that the bacteria is more deadly (or less deadly) to the mice when the sugar is present.
Just goes to show how little the FDA can even imagine to protect us against.
It gets worse. Apparently you can pass this off as "natural flavor" in the US:
http://nagaseamerica.com/news_release/treha-trehalose-availa...
Food labeling in the US is a joke. Find a country with stricter regulations and see how the same product is labeled there. You'll find all the shady ingredients and percentages that were either missing or only vaguely specified in the US version.
Specifically, as far as I can tell, this is how trehalose has to be labelled in the EU (article 2): http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A3...
Right but in this case trehalose is global..
It also goes to show that Soylent was (before 1.5 at least) a bad idea. I wonder if it still is, given that they switched one disaccharide (trehalose) for another (isomaltulose).
Is this more or less "foreseeable" than speculative execution side channel timing attacks?
If this is true, that confirms suspicious I've had that particular things in our diet can cause issues with gut flora. It's problematic for people because we have very little control over what gets added, and some additives end up everywhere.
I thought modern views on ulcers confirmed that view. Does it not?
I apparently had a south east Asian protozoan that I picked up in the late 1980's. Stomach issues went away after a 6 week course of a rather nasty anti-protozoan. That the issue would wax and wane and I was intolerant to dairy. But not after is what made me consider that.
So not just that some bug can mess you up, but that some bugs may well prefer certain chemicals in our diet. Eat a particular food and whatever starts growing and pumping out toxins or proteins your immune system has issues with.
So not just that some bug can mess you up, but that some bugs may well prefer certain chemicals in our diet. Eat a particular food and whatever starts growing and pumping out toxins or proteins your immune system has issues with.
I don't know about food science, but... In infosec for a while. Not surprised at all about the recent side channels. Spectre / Meltdown are novel, but not new.
Edit: I bet for people in the right field of medicine/research this is interesting but not a big surprise.
Edit: I bet for people in the right field of medicine/research this is interesting but not a big surprise.
Well, it could protect us by making all synthetic ingredients illegal. Because there's no way to really know that some novel ingredient is safe. But that ain't gonna happen.
You realize there are a number of naturally occurring chemicals that are deadly as well right?
Nonsense! Now let me go eat this small jar of apple seeds I have saved up from a month of an-apple-a-day.
Probably won’t hurt an otherwise healthy adult.
https://www.medicalnewstoday.com/articles/318706.php
https://www.medicalnewstoday.com/articles/318706.php
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And people have learned not to eat them, through trial and error. Just as we're learning not to eat trehalose ;)
“[Trehalose is] a disaccharide made up of two glucose molecules linked with a sturdy α,α-1,1-glucoside bond, and it’s naturally found in low levels in some bacteria, fungi, plants, and invertebrates.”
Oops.
Oops.
Sure, but who eats enough of those things to get enough to be problematic?
Virtually all of the trehalose in food products is synthetic.
Virtually all of the trehalose in food products is synthetic.
My point is that synthetic versus natural is not a particularly useful line to draw here. If someone had figured out how to get tons of this stuff from bacteria, we’d be in the exact same situation.
Originally, they'd been getting the sugar from yeast, but they borrowed enzymes from a soil bacterium to radically reduce the cost of manufacture. From the article: "...making it in large quantities was expensive—about $700 per kilogram. With tinkering, syrup scientists at Japan’s Hayashibara chemistry company finally figured out a novel enzymatic method to make it on the cheap from starch. The method brought costs down to just $3 per kilogram."
From the paper linked in the article:
"Although its usefulness was recognized, trehalose was not produced on an industrial scale until 1994. The conventional method for production, for example, extraction from yeast, had too low a yield andtoo high a cost to be used. In order to implement industrial production of trehalose, we have researchednew enzyme systems and have succeeded in isolating a novel enzyme system from a bacterial strainbelonging to the genus Arthrobacter sp. Q36 that was obtained from soil [1]. The system has been found to consist of two novel enzymes: malto-oligosyltrehalose synthase (or MTSase) and malto-oligosyltre-halose trehalohydorolase (or MTHase). In the first step, MTSase catalyzes the intramolecular transglycosylation of glucose residue at the reducing end of malto-oligosaccharide from α-1, 4 bond to α-1, 1 bond, then malto-oligosyltrehalose is produced. This contains trehalose residue at the end of the saccharide chain. Next, trehalose is liberated from malto-oligosyltrehalose by MTHase. This pathway needs no high-energy sugar derivative such as sugar phosphate or sugar nucleotide. And those enzymes can repeatedly act on α-1, 4 glucan to produce trehalose up to 80 % yield (Fig. 1). The trehalose production scheme that has been developed in our company is shown in Fig. 2. Starch is liquefied by a thermostable α-amylase and is debranched by isoamylase. The formed amylose is converted into trehalose by this system. The system involves two novel enzymes, MTSase and MTHase, which act on amylose or starch to produce trehalose efficiently. By this process, we have succeeded in reducing the production cost of trehalose to approximately one hundredth of its initial cost. The cost was reduced enough to permit a widespread application to many foods such as sweeteners and stabilizers. In addition, trehalose is also expected to be used for various applications in the fields of medicine and cosmetics."
From the paper linked in the article:
"Although its usefulness was recognized, trehalose was not produced on an industrial scale until 1994. The conventional method for production, for example, extraction from yeast, had too low a yield andtoo high a cost to be used. In order to implement industrial production of trehalose, we have researchednew enzyme systems and have succeeded in isolating a novel enzyme system from a bacterial strainbelonging to the genus Arthrobacter sp. Q36 that was obtained from soil [1]. The system has been found to consist of two novel enzymes: malto-oligosyltrehalose synthase (or MTSase) and malto-oligosyltre-halose trehalohydorolase (or MTHase). In the first step, MTSase catalyzes the intramolecular transglycosylation of glucose residue at the reducing end of malto-oligosaccharide from α-1, 4 bond to α-1, 1 bond, then malto-oligosyltrehalose is produced. This contains trehalose residue at the end of the saccharide chain. Next, trehalose is liberated from malto-oligosyltrehalose by MTHase. This pathway needs no high-energy sugar derivative such as sugar phosphate or sugar nucleotide. And those enzymes can repeatedly act on α-1, 4 glucan to produce trehalose up to 80 % yield (Fig. 1). The trehalose production scheme that has been developed in our company is shown in Fig. 2. Starch is liquefied by a thermostable α-amylase and is debranched by isoamylase. The formed amylose is converted into trehalose by this system. The system involves two novel enzymes, MTSase and MTHase, which act on amylose or starch to produce trehalose efficiently. By this process, we have succeeded in reducing the production cost of trehalose to approximately one hundredth of its initial cost. The cost was reduced enough to permit a widespread application to many foods such as sweeteners and stabilizers. In addition, trehalose is also expected to be used for various applications in the fields of medicine and cosmetics."
I agree. It was confusing to say "synthetic". What I meant was something like "food ingredients that would otherwise be present only in trace quantities".
What's problematic is how "Generally Recognized as Safe" (GRAS) has been redefined. Instead of "something that's historically been in food, and hasn't injured people", it's become "anything that isn't clearly toxic in short-term testing".
What's problematic is how "Generally Recognized as Safe" (GRAS) has been redefined. Instead of "something that's historically been in food, and hasn't injured people", it's become "anything that isn't clearly toxic in short-term testing".
If you're ultimately just looking for stricter standards before introducing something new (regardless of source) to the food supply, I could totally go for that. It's a tough question. I'm not sure if we can really call something "safe" with less than a century of testing, but I'm not sure if it's reasonable to require that. Maybe it is, do we really need new stuff in our food?
Yes, that was my point :)
Because it's very hard to prove negatives like "not harmful". In that there are just too many ways in which stuff can be harmful. So at best, FDA excludes the obviously-toxic stuff, and the rest is assumed safe, until there's evidence that it's not.
And yes, I don't want new stuff in my food. I avoid processed food, and prefer local "organic" (hate the word, but whatever) sources.
Because it's very hard to prove negatives like "not harmful". In that there are just too many ways in which stuff can be harmful. So at best, FDA excludes the obviously-toxic stuff, and the rest is assumed safe, until there's evidence that it's not.
And yes, I don't want new stuff in my food. I avoid processed food, and prefer local "organic" (hate the word, but whatever) sources.
In general, the FDA over-regulates rather than under regulates.
A comment is too short to summarize the reasons why, but I would refer interested people to Eliezer Yudkowsky's Inadequate Equilibria ― there is a 50 page dialogue between two humans and an alien visitor on the FDA.
A comment is too short to summarize the reasons why, but I would refer interested people to Eliezer Yudkowsky's Inadequate Equilibria ― there is a 50 page dialogue between two humans and an alien visitor on the FDA.
> the FDA over-regulates rather than under regulates.
It seems more accurate to say it does both simultaneously, or that it mis-regulates.
It fails to regulate some things that it should have (such as this), and it regulates other things that are better left alone.
And we should expect any noisy estimator to do that in general: there are always going to be both false positives and false negatives.
One thing we should be careful about though is to distinguish between arguments over the relative propensity of either, vs. the relative weighting that should be given to each.
E.g. sometimes people say 'no, the FDA over-regulates rather than under-regulates', when what they really mean is that the find that specific instances of over-regulation to be very harmful, while they think that the examples of under-regulation can be ignored.
It seems more accurate to say it does both simultaneously, or that it mis-regulates.
It fails to regulate some things that it should have (such as this), and it regulates other things that are better left alone.
And we should expect any noisy estimator to do that in general: there are always going to be both false positives and false negatives.
One thing we should be careful about though is to distinguish between arguments over the relative propensity of either, vs. the relative weighting that should be given to each.
E.g. sometimes people say 'no, the FDA over-regulates rather than under-regulates', when what they really mean is that the find that specific instances of over-regulation to be very harmful, while they think that the examples of under-regulation can be ignored.
> In general, the FDA over-regulates rather than under regulates.
I STRONGLY disagree. The FDA is underfunded and only looks into a tiny minority of cases deemed worth their effort. Walk into a "health" food store and look at how many unregulated drugs are on the shelf. They put out fires more often than they prevent them.
I STRONGLY disagree. The FDA is underfunded and only looks into a tiny minority of cases deemed worth their effort. Walk into a "health" food store and look at how many unregulated drugs are on the shelf. They put out fires more often than they prevent them.
Eliezer Yudkowsky is neither a bromatologist nor a pathologist, so as far as I' concerned his speculation on the subject has minimal value.
Here is a link to what this poster is talking about: https://equilibriabook.com/molochs-toolbox/
It appears to be another in a long line of entries in the "undergraduate economics solves all the world's problems" genre.
It appears to be another in a long line of entries in the "undergraduate economics solves all the world's problems" genre.
In this particular case it's "self-taught AI enthusiast solves all the world's problems," but yeah, same thing.
there is a 50 page dialogue between two humans and an alien visitor on the FDA.
I would recommend caution in using Yudkowsky's long-form fictional strawmen to do anything other than analyze his own cognitive biases.
I would recommend caution in using Yudkowsky's long-form fictional strawmen to do anything other than analyze his own cognitive biases.
> In general, the FDA over-regulates rather than under regulates.
In general, the FDA under-regulates dramatically.
In general, the FDA under-regulates dramatically.
WOW!
I had c. diff (it sucked, a lot) and this really fills in some gaps for me. Before my gut was destroyed by c. diff, I used to eat more ice cream, no doubt containing this sugar. Obviously I can't say for certain, but I can see how this helped the pathogen gain a hold in my gut.
I had c. diff (it sucked, a lot) and this really fills in some gaps for me. Before my gut was destroyed by c. diff, I used to eat more ice cream, no doubt containing this sugar. Obviously I can't say for certain, but I can see how this helped the pathogen gain a hold in my gut.
You said you "had" c. diff. How did you get rid of it?
Ended up getting the FMT.
So am I right to summarize that because of the type of sugar used which allows the ice cream to stay solid at a higher temperature, it was easier to have the deadly bacteria thrive on the type of sugar used?
Rather, two strains of C. Diff have enhanced trehalose metabolism. It’s 5e trehalose you eat which feeds it well, in your gut. The ice cream itself was/is safe in terms of pathogens.
Not only are the bacteria more likely to survive, they release more toxins when they are using trehalose. This might be a defensive mechanism based on the evolved assumption that presence of trehalose indicates the presence of competing hostile bacterial colonies.
We sure are guinea pigs. Maybe this kind of shit caused my thyroid autoimmune disease.
It was living downwind of a pesticide-ridden cabbage field that did it for me.
Hey, sorry for late reply. How are you managing your condition ?
Sorry for my even later reply. It took a couple surgeries to remove my thyroid and lymph nodes it had spread to. And a few rounds of radioactive iodine treatment and scans to get the parts that had spread through my lymphatic system. My last treatment was 10 years ago during high school and I've thankfully scanned clean since.
Management has been staying on a relatively high thyroid hormone replacement dose and periodic radioactive iodine scans. Worst case scenario, the scan requires a grueling couple weeks off of my medication and on a low-iodine diet so that any remaining thyroid cells are completely starved and ready to absorb the radioactive dose. Best case, the recombinant thyroid-stimulating hormone, Thyrogen, is available and my insurance is willing to pay for it because it reduces prep to a pre-scan injection.
Management has been staying on a relatively high thyroid hormone replacement dose and periodic radioactive iodine scans. Worst case scenario, the scan requires a grueling couple weeks off of my medication and on a low-iodine diet so that any remaining thyroid cells are completely starved and ready to absorb the radioactive dose. Best case, the recombinant thyroid-stimulating hormone, Thyrogen, is available and my insurance is willing to pay for it because it reduces prep to a pre-scan injection.
Citation: J. Collins, C. Robinson, H. Danhof, C. W. Knetsch, H. C. van Leeuwen, T. D. Lawley, J. M. Auchtung & R. A. Britton. Nature 2018-01-03 online.
Link: https://www.nature.com/articles/nature25178
DOI: 10.1038/nature25178
Abstract: Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.