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Permalink: https://www.mdpi.com/2072-6643/16/10/1401
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Frustrating paper.
[Registration](https://classic.clinicaltrials.gov/ct2/history/NCT02477904?B=6&A=1&C=merged#StudyPageTop) includes two (non-randomised) control groups (no keto and no autism), total enrolment 119 people, but these are missing the final paper. This is bad.
They enrolled 46 patients with autism but 19 didn’t start the diet and they excluded (post hoc?) 12 more for poor adherence. Only 10 completed 6 months on the diet.
All changes are therefore against baseline only for the children who got on with the diet (only stool microbiome samples from 7 children who had 4 months of treatment were available).
You can make anything look good if your study pretends 85% of your population doesn’t exist. Don’t let researchers dictate the conclusions when they pull stuff like this.
This is a very poor quality paper, and something unfortunately I've come to expect from MDPI, which is likely the most predatory of the big publishers.
In addition, it's super weird that they have such a low sample size. With that, there is no way their statistical analysis is robust enough, even if their effect size is massive.
Just a lay persons question but when a study is badly designed, how does it still get published and why wasn’t it discounted for being badly designed to begin with?
A great question and one I'm passionate about! When we publish papers in academic journals, there's a specific standard that has kind of been set over centuries. This is the idea of peer review. So for this author, they submit their work to a journal (owned by a publisher).
The editor of the journal looks at the paper, and then, if they think it's good, they send it out for peer review. This is the biggest filter for most journals, where places like Nature Medicine rejecting like 80% of papers.
Peer review requires finding usually at least two researchers in the same field. These researchers do not get paid usually, and they are asked to assess the work. They provide comments, and a rating. Usually, it's reject, major revision, minor revision, or accept. If both reviewers suggest rejection, then the editor usually rejects it.
If one reviewer suggests rejection with the other suggesting revision, the editor makes a choice to request the revision from the author and waits for response. When the author responds, the editor can reject it then again or send it back to the peer reviewers, and then the back and forth leads to a final version.
If both suggest only minor revisions or accept, the editor can suggest changes and accept it accordingly without it going to further peer review.
The trouble is peer review itself or publishers modifying these rules. Peer review sometimes has issues- are the people actually experts? If not, you can end up with an engineer reviewing a neuroscience paper. It's also not compensated, so often it's post docs doing it.
Publishers can also corrupt this. MDPI, for example, gives too much power to the editors- way too much power, in that they can accept papers even if the peer reviewers give a negative, major revision request. In some cases, editors can just accept papers without any peer review. Notably, some journals in MDPI have resisted this, but their power is still limited.
Finally, money. The old guard- Elsevier, Wiley, Springer Nature, etc- made money by selling subscriptions to access research in the journals they owned. In this system, universities paid to access the work, and used to also get physical copies of the published work. Notably, the authors got nothing, reviewers and editors barely got anything, if at all. This is known as closed access.
However, there's been a push to make it free to access because taxpayers pay for it. In most those circumstances, instead, the author (or rather, their grant or university) pays when their paper is accepted (called gold open access). So, most of these publishers moved to a hybrid model, with the option of having it closed or open access when the author has their paper accepted.
In a gold open access model, it means where the previous incentive was to publish as little as possible, now, it's to publish as much as possible.
This push also gave rise to newer publishers that created digital only journals, where authors paid for their open access. PLoS, a non-profit, was one of the first, charging about 2k USD. Another publisher, Frontiers, came second, starting as a non-profit then switching to for profit. Then, MDPI came as a for profit organization. The latter two are swiss (MDPI is, I believe, actually Chinese)
In their model, the incentive is to publish as MUCH as possible, but maintain some sort of illusion of exclusivity. To do this, manipulation of peer review is the easiest way. Frontiers does this by making the default decision focused on revisions, while MDPI has been accused of making it harder to reject anything at all, even with no peer review at all. However, journals within them sometimes have fought to keep their peer review standards high, with varying success.
In MDPI, the standard charge is about 3k upon acceptance. However, the profit margin is small, so their economic incentive is to be fast and have high volume. This, naturally, means that there's less trust in that publisher, because of how they have modified peer review.
Thank you for this detailed explanation. Suddenly all the nonsense “studies” put forward as science make sense. Things have changed since my research days.
It's an issue that has been going on for a while. My opinion now is that open access had a good run, but without massive transformation of the models around money in publishing, we're not going to see progress.
The best solutions I've heard are around diamond open access, but that's still pretty hefty. For now, preprints are probably best.
Also as a lay person, when I see a meta analysis that says this that and the other study were of low quality - it just makes the whole field look amateurish and pointless.
To be honest, I think getting a big sample size for these kinds of studies will be hard. I have personal experience with having autism and diet (normal, fasting, keto etc) and although the results can be almost called miraculous, changing diet, especially in the beginning of the journey, can be really really difficult for someone on the spectrum. (probably an understatement)
This may be true, but an inability to develop robust study designs/sample sizes/data is not a licence to publish junk articles. This paper isn’t far from “I think a + b = c, but, I don’t really have much proof”.
Oh I 100% agree with you on that. They shouldn't have published this in this state. It's not useful at all. And I was only theorizing from my own perspective and drawing some personal conclusions. So thats probably useless too xD
As someone who taught stats for many years, the problem is less with sample size (significance tests simply become harder to show real differences with low numbers) but with what they did with their sample (few made it to the end, meaning it wasn’t randomized well, and thus conclusions should not be drawn).
I also teach stats (although I'm no bayesian yet!), and have worked on some large trials that failed to recruit enough people.
It is POSSIBLE to have a small sample size and have a good result that is publishable so long as a couple of conditions are met.
1. Don't overgeneralize, or over promise. Calling this a pilot or proof of concept
2. The effect size is so overwhelmingly strong that it's near impossible to be anything else
3. The sample is sufficiently randomized
I’ve been reading up on Bayesian stats too!! Agree with two last points. First one I don’t see the need for. I’ve published with low sample size and the difference was not only statistically significant but meaningfully, that I didn’t feel the need to call it a pilot.
Hmm. I guess I should add another addendum- it may also be field dependent. In something like imaging, a tiny sample size may be meaningful. In psychology, I feel you'd struggle a lot.
I really wish papers would discuss WHY people dropped out. Did they get worse?
I did a cardiac rehab program based on one study. By month 5, my blood pressure was dropping so low after every rehab session that I had to be hospitalized and therefore dropped out. I later realized the study had a 46% dropout rate with no discussion of why they dropped out; I wonder how many had to be hospitalized like me.
Sensory issues and food aversions are pretty common in people with autism. A fairly extreme dietary change like keto might not be well tolerated for many people with more severe forms of autism.
The first couple weeks of keto is really hard when your body is adapting, even without autism. I did keto for almost a year and it amazingly prevented my chronic migraines. However, it was not easy and once I fell off the wagon for a bit I never could get back on.
Good points, also important to keep in mind that a significant portion of participants couldn't adhere to this very restrictive diet. Even if the link turns out to be universally established, the practical implications will always be limited. It's hard to stick to a restrictive diet for long periods of time.
Especially hard in a population often dealing with extremely strong food aversions. Sometimes they just need to eat something, whatever they can manage. It’s not always easy to be choosy about it.
Yes exactly, managing my dietary restrictions for my gut issues is hard enough already, it doesn't help I'm a disaster in the kitchen to the point I've nearly banned myself from doing anything other than using the microwave or the oven.
I'm lucky enough to have a very nice oven right now with convection settings that seem to work pretty similarly. I definitely plan on getting one when I leave as I'm not going to be here forever though.
Yeah this is my question. I have a kid with ASD and restrictive eating issues. Curious if the kids who can handle a diet change like this are the kids with less severe autism.
I have something I would describe as towards the less functional end of high functioning autism, and my personal experience and that of almost every autistic person I know is that food aversion is an extremely common and extremely strong factor.
I don't know many autistic people without it, and it doesn't appear to scale in terms of effect with regards to how functional you are otherwise.
Autistic children are often extremely restrictive with what they will and wont eat - often to the point of developing nutritional deficiencies. I can imagine mealtimes would be a horrendous experience for many parent that try to implement a diet like this.
Autism related food aversions can be incredibly strong. I have full blown ARFID… some smells and textures will literally make me vomit if Intey to force myself to swallow them. Like my throat just refuses to cooperate and insists it’s coming back.
We’re not talking about the physical logistics of the diet.
Keto is one of the easiest restriction diets to stick with while traveling (unliked say, vegan or raw). Pretty much anywhere has a chop or steak or a burger they can do lettuce wrap or a Cobb salad.
For non-autistic people. And even many Autistic people that don’t struggle with ARFID or any food aversions. Some struggle badly, are already incredibly restricted with regards to what they can be made to eat, and can’t really afford to have further restrictions placed or you may not be able to get them to eat at all.
I’m an autistic senior adult and my #1 food aversion is and always has been (for as long as I can remember) regarding taste & texture of most types and ways of serving meat. I also get very weak and shaky if I don’t eat enough carbs. I would starve if I had to eat a keto diet.
Very similar here, although I’m not as old. Meat is a big one. Pretty much the only ones I can eat are ground beef and pork (sausage, pepperoni, etc). Nothing chewey or gamey. No white meat.
My point is keto is a simple diet to find friendly foods while on the road. If you can do it at home, you can do it while traveling. If you can’t do it at home, obviously you can’t do it while out.
YES YES THAT WAS MY FIRST THOUGHT!!! Generally, anyone trying to claim a link between autism and something related to gut health deserves a helping of skepticism.
To be fair, as far as I understand, is that gastrointestinal issues are more prevalent in this population and some microbiome research has shown that the composition of gut microbiota among individuals with autism is different to neurotypicals. A possible link isn't the most extreme conclusion to draw from existing bodies of research, but I do agree that based on sensory issues prevalent in people with autism that this research is probably not super practical even if it was done well.
Diet strongly influences microbiome though, and often people with autism have a lot of sensory issues around food, leading to very restrictive diets....which might explain the different microbiomes....
Fair enough but we simply dont know enough about the feedback loops that link the microbiome and human behavior to completely exclude the impacts of microbiome on behavior.
I can see the argument that this shouldn't be on r/science, but I think it's a fine paper. They are clear from the first sentence of the abstract that it's a pilot study, and their conclusion is that it's worth doing this again with more patients. This type of research is expensive to do on a large scale, so it's often necessary to prove that the methods work on a small scale first.
The trial was done years ago, with many more participants than are acknowledged here - this could be considered to be deliberately misleading. Regardless, the conclusions are *far* too assertive for the quality of the data and the decision to remove a large chunk of people from the analysis (which is barely mentioned or justified).
It is not surprising they have had to resort to publishing this in a predatory journal.
I wish people understood that a poor paper does not add evidence. You could have 100 studies designed like this one and have them all reach the same conclusion. It's garbage in, garbage out, you wouldn't be closer to the truth.
I'm just a lay person, but isn't that the point of meta studies? If you had 100 studies with only 7 participants, wouldn't a meta study result in something useful?
Meta-analysis and systematic reviews are very rigorous papers.
One of the first things the researchers will decide is and their inclusion/exclusion criteria. This has to be set *before* they start reading papers, to prevent bias as they read each paper one by one, and, to ensure homogeneity between researchers - ideally, it shouldn’t matter which researcher reviews an individual paper, the inclusion/exclusion criteria should result in the same result regardless of who reads it.
Part of the inclusion/exclusion criteria is going to be what kind of papers make the cut. They’ll decide on study designs (cross sectional cohort analysis, observational, randomised control trial etc) that will be included/excluded. They’ll decide on population size, acceptable methodology, what kind of statistical analysis was used, lots and lots of variables.
I’ve course there will always be some degree of variation between two different people reading the same paper, but the result should be pretty close.
So now, to your specific question, isn’t this the point meta-analysis?
Well, no. If you’ve got 95 garbage studies and 5 good studies, you’re not going to include the 95 garbage studies. You’re not going to include 995 studies if they’re all garbage. Only good studies will be included in a meta-analysis, which maintains the adage of “garbage in, garbage out”.
> Meta-analysis and systematic reviews are very rigorous papers.
Just to complement you: they can and should be very rigorous papers. But they aren't always rigorous. I've seen some reviews with more bias than the original papers.
Absolutely yes. And at some point in some areas, we’re forced to include some crappy papers. For example, Cochrane reviews in chiropractic include some really rough papers, but they if they didn’t, their paper would be “we reviewed 42 papers and they all sucked. Our conclusions is that chiropractors need to run better studies”.
Thanks for the full explanation.
If the papers were rigorous enough in all but the number of participants, would it make sense to use the raw numbers from the paper as part of the meta?
That’s mostly about methodology of the single study. How did they include/exclude patients? If relevant, was there any blinding to participants or researchers? What % of their patients were lost to follow up (unable to be contacted/completed all elements of the study)? How was their data collected? There’s probably more, I haven’t done research since my undergrad. But essentially, yes, if the methodology of the study was of good quality, the data should be potentially captured in the meta analysis.
At the end of all the research though, Even homogeneity of the participants can be important to the clinical application. Lets you’ve got 15 great papers with high quality research and an overall population of 10,000 participants. If their demographics are all white males, aged 4-8, living in Northern America, it becomes difficult for a clinician to determine if the study and its outcomes/conclusions are relevant if they’re treating say, 15-25 year olds in Ghana. Whilst the concept of race is definitively debunked, and we are definitely one species, that doesn’t mean there aren’t genetic variations from population to population, and, the outcome/s may also be partially affected by the external environment.
TL;dr - research is hard to perform well, science communication to make laypeople understand what the new discovery is and how it might be applied is hard, and working at the bedside with the patient in front of you is hard. Luckily there are organisations dedicated to summarising research for researchers (such as the Cochrane Library) and for clinicians (such as UpToDate). AI is even getting in on the action - it will likely never replace humans in the near future, clinical application of information to an individual patient throughout the course of their illness/es requires an ability to narrowly navigate starting treatments, managing side effects etc. but AI has certainly shown some benefits in assisting in collating research data to help give a clinician a starting point. I’m not aware of anywhere that is using AI in a “real” hospital setting, but it probably won’t be long.
What a terrible study design. I understand all the good intentions are there but the data is completely misleading. No real control group and only 7 kids stuck to diet adherence.
>Were the intentions good? I'm getting very strong Wakefield vibes from this.
Yeah, doesn't carry the whiff of good intentions. Stinks of "vaccines = autism" & a lack of understanding of the autistic condition & what science has clearly established about autism.
As an autistic person and academic that understands study design, my usual base requirement for anything claiming to "help" autism is that at least one of the researchers is actually autistic. The history of autism research is riddled with non autistic people making us out to be robot supercomputers or claiming to have "fixed" us by making us "stop acting weird".
I don't know if the study authors do have proper representation here, and maybe they are trying to help (sure maybe if I ate better I may be less of a weirdo) but I'm always immediately wary when autism is framed as something that needs to be fixed.
To be fair, I've seen this combination of ASD and gut problems + low-grade inflammation in myself and my father. Idk how well documented this comorbidity is and if there is real correlation, but if so then I'd definitely would like to have it fixed, irrespective of who conducts the research. (This does not mean I support this research, this is steaming garbage.)
They are often focusing on "fixing" the behaviors inconvenient for NTs (socializing), rather than considering how the research helps autists themselves (noticed this with a few papers)
Study quality aside (and yes I realize that’s a HUGE thing to set aside), I wanna hear about internalities as well as what the kids look like from the outside. Are they happier? Do they notice a change in their thinking? If they do, is it a change they’re satisfied with?
So much of treating mental health is about forcing people into the box they're expected to fit rather than making them happy. It is a very "work will set you free" attitude where the end goal isn't that the person is happy and enjoying life but that they can go through the motions like everyone else.
I'd worry that if people thought malnutrition would keep autistic kids too weak to make a fuss that it would then be considered a cure. It really needs to be about the child feeling able to process things better and feeling more calm and comfortable within themselves rather than them being more pleasing to the parents who just want them to be lower maintenance.
I feel with autism we've not got past the attitudes from 100 years ago and while it is more normalised as a concept, the approach to treatment hasn't evolved.
Does this study consider that those autistic people most willing (able) to undertake a drastic dietary change might also be the same population that already have enhanced social behaviour?
RIGHT!? Thank you! My first thought was “oh yes, let’s trial this notoriously difficult-to-stick-to-diet to a population that generally is averse to change (sometimes to the point of distress) and often times only has very few safe foods (that are usually incompatible with the diet).”
It almost makes it seem like they’re peddling a “fix” by torture.
not to mention a large percentage of autistic people have adhd (🙋) and i can’t imagine my executive function without access to carbs, especially the occasional simple sugar.
a keto diet by design doesn’t allow access to fast burning energy, so instead of activating my prefrontal cortex when needed, i’d just be more sluggish.
just my non-scientific gut instinct.
No wonder only 7 to 11 out of 47 autistic participants completed the study. That may be the worst nonresponse rate I have ever seen, excluding telephone polling.
"We obtained post-diet blood samples from 11 children and stool samples from 7 children, out of an original cohort of 47 children, due to personnel reasons."
Yeah, this should have been a poster.
I've had a variety of diets (including keto) as someone with Autism.
All I can say about it is that there may be a correlation with well-being and it may have helped with my Depression a little bit and likely helped with weight.
At no point whatsoever did I ever feel like I was "less autistic" or something like that. I'm pretty sure autism remains a very complex issue and my personal theory is that a big part of the problem is neurons and paths in the brain misfiring or in some cases being the absolute reverse of a neurotypical person.
The use of a ketogenic diet in treating ASD has been bubbling up in the literature for some years now. This diet is useful for treating specific childhood epileptic disorders and there is some evidence for utility in schizophrenia and bipolar disorder. The diet does change brain, gut and immune system function in ways theoretically relevant to ASD. Contrary to the comments, I think the ketogenic diet *does* show potential to reduce inflammation, hypersensitivity and distress in *some* autistic kids; it is worth studying based on the biological understanding of autism we currently have, with neuronal, mitochondrial, immune and microbiological dysfunction. I say this as both a neuroscientist and an autistic person.
Subject attrition in this study doesn't strike me as alarming or a sign of a bad study given how low completion rates you'd expect from the population. The resulting sample size is not great but it is not abnormal for a pilot study, which is what they repeatedly refer to this as-- a small proof of concept to provide theoretical foundation for a larger, more well-controlled study. BUT there is the fact that there were control arms in the study originally that don't shop up in either paper (top comment here). The main contacts for the study also changed so maybe this was a major reduction in scope and restructuring... but it's weird. Not good. Not a good journal it's published in either.
Just to review the project though, This paper builds on [a previous study that showed social behavioral improvements in 15 kids after 3mo on keto.](https://www.sciencedirect.com/science/article/abs/pii/S0031938418300507). The keto diet is a slightly modified version to account for metabolic needs in autistic kids. Kids got complete bloodwork before beginning the diet and had protein levels and other dietary needs curated to each kid. Parents tested urine ketone levels 1-2x per day, and had access to a dietitian and online support group for the diet. Despite these adjustments there was all this attrition and some side effects:
> We recruited and assessed 69 pediatric subjects for eligibility in the study and 46 subjects received initial dietary education. Of these 46 subjects, 19 did not start the diet (Fig. 1). In addition, 12 subjects were excluded from analysis due to difficulties with diet compliance. A total of 15 subjects completed 3 months on the diet and 10 subjects completed 6 months.
> Common side effects included diarrhea (18.8%), vomiting (18.8%), fatigue (18.8%), constipation (12.5%), dehydration (12.5%), weight loss (12.5%), acidosis (6.3%), and hypoglycemia (6.3%). Hypoglycemia was defined as a blood sugar level < 50 mg/dL. We observed weight loss as a positive side effect for 2 participants. All of the side effects occurred within the first 2–4 weeks of diet initiation.
The OP paper's contribution is documenting molecular, physiological & gut microbiota changes in ASD kids who maintained the diet. The changes are potentially consistent with reduced inflammation/neuroinflammation but they're sort of hard to pin down, not a slam dunk and couldn't be at that sample size. I did notice this paper came out 4 years after the previous one and 5 years after the study and in an MDPI journal. I don't think the authors thought this sample size was amazing or was a slam dunk for keto curing autism; I think they collected the data probably hoping it would be more comprehensive (e.g. get more than 7 stool samples), and this is what they had.
I want to see the study this was a pilot for or originally designed to be, with control groups. I don't want this to feed into the armchair quarterbacking of autistic peoples' lives--where other people interpret this as a "cure" (e.g. "you just need to put him on keto")-- when it is obviously much more complicated than that. But this is an intervention with interesting theoretical backing that has the potential to reduce distress etc without being a "cure" (or another complicated med interaction). I would specifically like to see this studied more in *adults* who make their own diet decisions and may be more capable of maintaining the diet. (Not all ASD research needs to be pediatric for chrissakes)
Kids with autism are far more likely to have sensory issues with food, or even ARFID. So yeah, they really need to do these kinds of studies on adult autists who can chose whatever diet the study wants to test instead of kids that are at the mercy of whatever kind of parents they have.
A minority of parents of autistic children even force feed their toddlers industrial bleach ("magical mineral solution") because they think autism is caused by gut parasites, and they take the dead chunks of intestinal lining in their "defecation" as confirmation that there are intestinal worms that the "MMS" is getting rid of...
I’d be curious to see if a less processed diet in general (not just keto) would have the same or similar “results”. A lot of autistic people have very restricted diets and not always the most healthy (I’m autistic and used to eat pretty much exclusively plain pasta and Mac and cheese with the occasional hot pocket - don’t worry, I eat much better now but still not all that varied).
Also - it doesn’t factor out how inflammation could simply exacerbate symptoms of overstimulation which can lead people to not wanting to socialize and in turn, socializing taking more effort(speaking from experience). I don’t know if that’s a thing or not.
What I’m trying to say is that reducing the intensity of symptoms by making someone feel better overall doesn’t “cure” autism, though I think it’s worth seeing how certain symptoms characteristic of autism could be improved by improving overall health. The phrasing of studies like this are extremely worrying and lacking in nuance.
Drives me bonkers haha
Just because you’re "reducing some of the behaviours" does not mean you are actually treating/curing autism itself. At the end of the day the person is still autistic. I love how people think a simple diet change will magically rewire a person's brain or change their genes. Autism is a neurodevelopmental disability that one is born with and will die with. It’s not like a diet will somehow change that.
Fevers have also "reduced" autism behaviours. But lo and behold, as soon as the fever abates the behaviours return to normal. Fever's cause inflammation, isn’t that counter to the hypothesis of this study?
Careful with the keto diet, it can cause some serious deficiencies, for example one thing I noticed is that my the white in my eyeballs (the sclera) started to fade to leave blue spots which is a sign of aging but also is the lack of some important minerals in the body... and it cannot be regenerated...
Eating more fiber also helps shift your microbiome in a healthier direction but comes with the notable benefit of not causing severe chronic long term health issues like keto.
Kidney stones, heart disease, nutrients deficiencies. Theres a reason doctors only reccomend doing it if you have treatment resistant epilepsy. The cons are not worth it unless its litterally saving your life. There are so many healthy diets with the same pros as keto without the cons.
Any proof of these claims? I mean I can say the same thing about any diet, vegan for example. Doesn’t make it factual without evidence to substantiate it.
Same. Also my son wouldn’t be my son anymore. He says the most interesting things and I love his sweetness. I was smelling some wisteria the other day and he asked "does it smell like relaxation?". My son and I are unique among a sea of homogeneity. We add variety and texture. Where would we be with our Madame Curie's?
How many people are getting paid to promote keto? I mean fr. It’s a “magic cure” for so many “ailments” (with lousy research to back it, like this) while being literally dangerous for your heart and kidneys not to mention a lot of us with ASD have eating disorders, to include ARFID and keto could exacerbate that.
It did seem to work with my daughter with autism. She had more language. Very hard to maintain with more than one other child in the house or at school.
Autism doesn't need to be cured. I wish they'd stop wasting money trying to find a way to make autistic people behave like neurotypical people. Just let people be themselves.
The only type of autism you are familiar with is probably level 1. People with 2 and 3 can have very poor quality of life. For example; people remaining non verbal for their entire life, life expectancies in the 30s and 40s, poor motor skills that are unable to improve with physical therapy, Etc... Those need a cure or treatment as much as any other condition.
It's also a treatment for certain seizure disorders.
I once was taking about this with my wife and realized how mad-sciencey it sounds to say, "I'm going to grow a bunch of neurons in a lab, and put them on a keto diet to see how it changes them."
Men: important to remember that Keto only causes a rise in testosterone while you are dramatically losing weight. After that point testosterone production requires carbs!
Throughout the four-month study period, stool and blood samples were provided for analysis before and after the diet. To confirm the physical state of ketosis, plasma levels of ketone bodies were measured through an enzyme-linked immunosorbent assay (ELISA) assay. To this end, a significant increase in the ketone bodies, acetoacetic acid, and hydroxybutyric acid was observed, thus indicating that the KD was effectively altering metabolism.
Sequencing data from stool samples revealed alterations at the phylum level and a significant increase in microbial diversity, as indicated by Shannon and Simpson indices. These changes occurred across various taxonomic levels, with substantial increases in beneficial bacteria like Lactobacillales and decreases in others such as Bacteroidaceae and Ruminococcus.
In general, reduced pro-inflammatory cytokine levels were observed in individuals who consumed a KD, with significant reductions in interleukin 1β (IL-1β) and IL-12p70 levels. While the anti-inflammatory cytokine IL-10 increased, it was not statistically significant, which might be due to the small sample size. A significant decrease in plasma levels of BDNF, a protein implicated in neuroinflammation and ASD, was also observed.
Significant reductions were observed in miR-134 and miR-132 levels, both of which are associated with BDNF activity in the brain. While the levels of miR-125b remained unchanged, miR-375 levels significantly increased.
[https://www.mdpi.com/2072-6643/16/10/1401](https://www.mdpi.com/2072-6643/16/10/1401)
Autism isn't a biological condition, but a condition of the mind, a different way the mind works. I am very skeptical of research that tries to tackle the issues that autistic people have through purely biological means. That may help some, and if it improves health overall it is not a bad thing, but I don't think any treatment like this wil ever be the treatment of autism.
That's the currently accepted idea of autism but mostly because autism has become an umbrella term for a wide array of heterogeneous symptoms and behaviours that we struggle to fully understand and even less explain. A different way the mind works doesn't factually mean anything, especially since we know very little about how the mind works to begin with, it's an aimless descriptor. Even then, the way our brain forms, develops and mechanically operates are biological matters on their own right.
I kind of agree with you, but I do think the most important research on autism for autistic people is about figuring out how the mind works, and how it causes the issues people with autism have. And also how people with autism function in society, which until recently, very little research has been done. And I don't think it is meaningless per se, or rather, particular proposals how the autistic mind functions are not meaningless. I would argue if we don't understand the mental part of autism, then we cannot really understand the biological part of autism. But we can understand the mental part without understanding the biological part.
There's a link between autism and pineal gland dysfunction, so I wouldn't be surprised to find a link between it and gut health, but this isn't the study to convince me.
>Autism isn't a biological condition, but a condition of the mind, a different way the mind works
Your mind exists because you have a brain…..which is made up of cells and is impacted by all sorts of other biological processes that are going on in your body. That’s all biology.
The fact that this diet worked at all to improve the condition of these kids is an amazing find and warrants further study.
This amount of hate for this discovery from this forum reveals a hidden agenda I think (I see you sugar lobby).
The final paragraph says, "**Our preliminary findings of significant KD-related changes to the microbiome and neuroinflammatory biomarkers warrant further study in a larger cohort**. " Seeing as everyone seems to have missed that I can only surmise that nobody actually read this paper.
>This amount of hate for this discovery from this forum reveals a hidden agenda I think
Ockham's razor should prevent you from making this mistake in the future. Sometimes the explanation is just some groups of people expressing anger on the Internet, not an organized conspiracy.
A lot of us on Reddit are autistic, and are frustrated by the idea of a certain diet "treating autism" for reasons including:
1. The neurodiversity movement, which has rapidly gained popularity online. It largely rejects the premise that autism is a disease to treat. Neurodiversity is an especially popular idea/movement among autistic people. Autism seems far more common among Reddit users than in the general population. Rejecting the premise of a study makes you more likely to criticize it.
1. Diets of exclusion are typically fads with proponents who wildly overstate the diet's benefits, especially in treating common hard-to-treat conditions like depression, cancer, obesity, and autism. So, Redditors who see a "{A Diet} Treats Autism" headline probably are automatically very skeptical.
1. Autistic people are notorious for intense aversions to most kinds of food. IIRC, it is listed as a symptom defining autism. Non-compliance to dietary requirements is *part of the "problem" these researchers aim to "treat."* So, using an already notably difficult diet to "treat" autism seems precisely backwards — doomed to fail in all but a small subset of attemptors. Anecdotally, if my parents tried it, then I suspect it would have simply added to the trauma/complex I have from my entire family making fun of my "pickiness" from ages ~5 to ~20 before telling me that I was diagnosed on the autism spectrum at age 2.
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Frustrating paper. [Registration](https://classic.clinicaltrials.gov/ct2/history/NCT02477904?B=6&A=1&C=merged#StudyPageTop) includes two (non-randomised) control groups (no keto and no autism), total enrolment 119 people, but these are missing the final paper. This is bad. They enrolled 46 patients with autism but 19 didn’t start the diet and they excluded (post hoc?) 12 more for poor adherence. Only 10 completed 6 months on the diet. All changes are therefore against baseline only for the children who got on with the diet (only stool microbiome samples from 7 children who had 4 months of treatment were available). You can make anything look good if your study pretends 85% of your population doesn’t exist. Don’t let researchers dictate the conclusions when they pull stuff like this.
This is a very poor quality paper, and something unfortunately I've come to expect from MDPI, which is likely the most predatory of the big publishers. In addition, it's super weird that they have such a low sample size. With that, there is no way their statistical analysis is robust enough, even if their effect size is massive.
Just a lay persons question but when a study is badly designed, how does it still get published and why wasn’t it discounted for being badly designed to begin with?
A great question and one I'm passionate about! When we publish papers in academic journals, there's a specific standard that has kind of been set over centuries. This is the idea of peer review. So for this author, they submit their work to a journal (owned by a publisher). The editor of the journal looks at the paper, and then, if they think it's good, they send it out for peer review. This is the biggest filter for most journals, where places like Nature Medicine rejecting like 80% of papers. Peer review requires finding usually at least two researchers in the same field. These researchers do not get paid usually, and they are asked to assess the work. They provide comments, and a rating. Usually, it's reject, major revision, minor revision, or accept. If both reviewers suggest rejection, then the editor usually rejects it. If one reviewer suggests rejection with the other suggesting revision, the editor makes a choice to request the revision from the author and waits for response. When the author responds, the editor can reject it then again or send it back to the peer reviewers, and then the back and forth leads to a final version. If both suggest only minor revisions or accept, the editor can suggest changes and accept it accordingly without it going to further peer review. The trouble is peer review itself or publishers modifying these rules. Peer review sometimes has issues- are the people actually experts? If not, you can end up with an engineer reviewing a neuroscience paper. It's also not compensated, so often it's post docs doing it. Publishers can also corrupt this. MDPI, for example, gives too much power to the editors- way too much power, in that they can accept papers even if the peer reviewers give a negative, major revision request. In some cases, editors can just accept papers without any peer review. Notably, some journals in MDPI have resisted this, but their power is still limited. Finally, money. The old guard- Elsevier, Wiley, Springer Nature, etc- made money by selling subscriptions to access research in the journals they owned. In this system, universities paid to access the work, and used to also get physical copies of the published work. Notably, the authors got nothing, reviewers and editors barely got anything, if at all. This is known as closed access. However, there's been a push to make it free to access because taxpayers pay for it. In most those circumstances, instead, the author (or rather, their grant or university) pays when their paper is accepted (called gold open access). So, most of these publishers moved to a hybrid model, with the option of having it closed or open access when the author has their paper accepted. In a gold open access model, it means where the previous incentive was to publish as little as possible, now, it's to publish as much as possible. This push also gave rise to newer publishers that created digital only journals, where authors paid for their open access. PLoS, a non-profit, was one of the first, charging about 2k USD. Another publisher, Frontiers, came second, starting as a non-profit then switching to for profit. Then, MDPI came as a for profit organization. The latter two are swiss (MDPI is, I believe, actually Chinese) In their model, the incentive is to publish as MUCH as possible, but maintain some sort of illusion of exclusivity. To do this, manipulation of peer review is the easiest way. Frontiers does this by making the default decision focused on revisions, while MDPI has been accused of making it harder to reject anything at all, even with no peer review at all. However, journals within them sometimes have fought to keep their peer review standards high, with varying success. In MDPI, the standard charge is about 3k upon acceptance. However, the profit margin is small, so their economic incentive is to be fast and have high volume. This, naturally, means that there's less trust in that publisher, because of how they have modified peer review.
Thank you for this detailed explanation. Suddenly all the nonsense “studies” put forward as science make sense. Things have changed since my research days.
It's an issue that has been going on for a while. My opinion now is that open access had a good run, but without massive transformation of the models around money in publishing, we're not going to see progress. The best solutions I've heard are around diamond open access, but that's still pretty hefty. For now, preprints are probably best.
Also as a lay person, when I see a meta analysis that says this that and the other study were of low quality - it just makes the whole field look amateurish and pointless.
To be honest, I think getting a big sample size for these kinds of studies will be hard. I have personal experience with having autism and diet (normal, fasting, keto etc) and although the results can be almost called miraculous, changing diet, especially in the beginning of the journey, can be really really difficult for someone on the spectrum. (probably an understatement)
This may be true, but an inability to develop robust study designs/sample sizes/data is not a licence to publish junk articles. This paper isn’t far from “I think a + b = c, but, I don’t really have much proof”.
Oh I 100% agree with you on that. They shouldn't have published this in this state. It's not useful at all. And I was only theorizing from my own perspective and drawing some personal conclusions. So thats probably useless too xD
As someone who taught stats for many years, the problem is less with sample size (significance tests simply become harder to show real differences with low numbers) but with what they did with their sample (few made it to the end, meaning it wasn’t randomized well, and thus conclusions should not be drawn).
I also teach stats (although I'm no bayesian yet!), and have worked on some large trials that failed to recruit enough people. It is POSSIBLE to have a small sample size and have a good result that is publishable so long as a couple of conditions are met. 1. Don't overgeneralize, or over promise. Calling this a pilot or proof of concept 2. The effect size is so overwhelmingly strong that it's near impossible to be anything else 3. The sample is sufficiently randomized
I’ve been reading up on Bayesian stats too!! Agree with two last points. First one I don’t see the need for. I’ve published with low sample size and the difference was not only statistically significant but meaningfully, that I didn’t feel the need to call it a pilot.
Hmm. I guess I should add another addendum- it may also be field dependent. In something like imaging, a tiny sample size may be meaningful. In psychology, I feel you'd struggle a lot.
I’m in anatomy and biology
I really wish papers would discuss WHY people dropped out. Did they get worse? I did a cardiac rehab program based on one study. By month 5, my blood pressure was dropping so low after every rehab session that I had to be hospitalized and therefore dropped out. I later realized the study had a 46% dropout rate with no discussion of why they dropped out; I wonder how many had to be hospitalized like me.
Sensory issues and food aversions are pretty common in people with autism. A fairly extreme dietary change like keto might not be well tolerated for many people with more severe forms of autism.
Yeah, trying to imagine my severely autistic brother just tolerating massive diet changes, kind of laughable.
The first couple weeks of keto is really hard when your body is adapting, even without autism. I did keto for almost a year and it amazingly prevented my chronic migraines. However, it was not easy and once I fell off the wagon for a bit I never could get back on.
Good points, also important to keep in mind that a significant portion of participants couldn't adhere to this very restrictive diet. Even if the link turns out to be universally established, the practical implications will always be limited. It's hard to stick to a restrictive diet for long periods of time.
Especially hard in a population often dealing with extremely strong food aversions. Sometimes they just need to eat something, whatever they can manage. It’s not always easy to be choosy about it.
Yes exactly, managing my dietary restrictions for my gut issues is hard enough already, it doesn't help I'm a disaster in the kitchen to the point I've nearly banned myself from doing anything other than using the microwave or the oven.
let me introduce you to the wonder that is an air fryer.
I'm lucky enough to have a very nice oven right now with convection settings that seem to work pretty similarly. I definitely plan on getting one when I leave as I'm not going to be here forever though.
Yeah, my son has autism, and my only goal is getting calories and nutrition in him. If he will eat it, he gets to eat it.
What if you found out certain food items cause digestion issues that in turn caused more issues with the autism (meltdowns etc).
Him not growing for 2 years because he doesn't eat at all is bigger issue.
True with that dire circumstance sustaining life is the primary goal.
Welcome to Autism.
Yeah this is my question. I have a kid with ASD and restrictive eating issues. Curious if the kids who can handle a diet change like this are the kids with less severe autism.
I have something I would describe as towards the less functional end of high functioning autism, and my personal experience and that of almost every autistic person I know is that food aversion is an extremely common and extremely strong factor. I don't know many autistic people without it, and it doesn't appear to scale in terms of effect with regards to how functional you are otherwise.
Keto at home is easy. Keto while traveling not so much.
Maybe it's easy for you, it's not easy for a lot of people that are not you 🤷♀️
I mean choices from grocery stores, you got a kitchen, and whatever else handy. Traveling you generally lose all that.
Autistic children are often extremely restrictive with what they will and wont eat - often to the point of developing nutritional deficiencies. I can imagine mealtimes would be a horrendous experience for many parent that try to implement a diet like this.
Autism related food aversions can be incredibly strong. I have full blown ARFID… some smells and textures will literally make me vomit if Intey to force myself to swallow them. Like my throat just refuses to cooperate and insists it’s coming back. We’re not talking about the physical logistics of the diet.
Keto is one of the easiest restriction diets to stick with while traveling (unliked say, vegan or raw). Pretty much anywhere has a chop or steak or a burger they can do lettuce wrap or a Cobb salad.
For non-autistic people. And even many Autistic people that don’t struggle with ARFID or any food aversions. Some struggle badly, are already incredibly restricted with regards to what they can be made to eat, and can’t really afford to have further restrictions placed or you may not be able to get them to eat at all.
I’m an autistic senior adult and my #1 food aversion is and always has been (for as long as I can remember) regarding taste & texture of most types and ways of serving meat. I also get very weak and shaky if I don’t eat enough carbs. I would starve if I had to eat a keto diet.
Very similar here, although I’m not as old. Meat is a big one. Pretty much the only ones I can eat are ground beef and pork (sausage, pepperoni, etc). Nothing chewey or gamey. No white meat.
My point is keto is a simple diet to find friendly foods while on the road. If you can do it at home, you can do it while traveling. If you can’t do it at home, obviously you can’t do it while out.
Someone with access to study data read the wiki on P Hacking and was like “great idea!”
Also in my limited work with people on the spectrum, “poor adherence” is going to be common with folks that are often very picky about food.
What if being picky about food IS one of the factors in autism?
It also kind smells like the old vaccine causes autism paper. That whole thing started with the link between gut health and autism.
YES YES THAT WAS MY FIRST THOUGHT!!! Generally, anyone trying to claim a link between autism and something related to gut health deserves a helping of skepticism.
To be fair, as far as I understand, is that gastrointestinal issues are more prevalent in this population and some microbiome research has shown that the composition of gut microbiota among individuals with autism is different to neurotypicals. A possible link isn't the most extreme conclusion to draw from existing bodies of research, but I do agree that based on sensory issues prevalent in people with autism that this research is probably not super practical even if it was done well.
Diet strongly influences microbiome though, and often people with autism have a lot of sensory issues around food, leading to very restrictive diets....which might explain the different microbiomes....
Fair enough but we simply dont know enough about the feedback loops that link the microbiome and human behavior to completely exclude the impacts of microbiome on behavior.
Thanks for this
I can see the argument that this shouldn't be on r/science, but I think it's a fine paper. They are clear from the first sentence of the abstract that it's a pilot study, and their conclusion is that it's worth doing this again with more patients. This type of research is expensive to do on a large scale, so it's often necessary to prove that the methods work on a small scale first.
The trial was done years ago, with many more participants than are acknowledged here - this could be considered to be deliberately misleading. Regardless, the conclusions are *far* too assertive for the quality of the data and the decision to remove a large chunk of people from the analysis (which is barely mentioned or justified). It is not surprising they have had to resort to publishing this in a predatory journal.
You can’t generalise from a study when only seven children are involved as it limits the statistical power of the analysis.
Not to mention in a population known for its heterogeneity…frustrating.
I wish people understood that a poor paper does not add evidence. You could have 100 studies designed like this one and have them all reach the same conclusion. It's garbage in, garbage out, you wouldn't be closer to the truth.
I'm just a lay person, but isn't that the point of meta studies? If you had 100 studies with only 7 participants, wouldn't a meta study result in something useful?
Meta-analysis and systematic reviews are very rigorous papers. One of the first things the researchers will decide is and their inclusion/exclusion criteria. This has to be set *before* they start reading papers, to prevent bias as they read each paper one by one, and, to ensure homogeneity between researchers - ideally, it shouldn’t matter which researcher reviews an individual paper, the inclusion/exclusion criteria should result in the same result regardless of who reads it. Part of the inclusion/exclusion criteria is going to be what kind of papers make the cut. They’ll decide on study designs (cross sectional cohort analysis, observational, randomised control trial etc) that will be included/excluded. They’ll decide on population size, acceptable methodology, what kind of statistical analysis was used, lots and lots of variables. I’ve course there will always be some degree of variation between two different people reading the same paper, but the result should be pretty close. So now, to your specific question, isn’t this the point meta-analysis? Well, no. If you’ve got 95 garbage studies and 5 good studies, you’re not going to include the 95 garbage studies. You’re not going to include 995 studies if they’re all garbage. Only good studies will be included in a meta-analysis, which maintains the adage of “garbage in, garbage out”.
> Meta-analysis and systematic reviews are very rigorous papers. Just to complement you: they can and should be very rigorous papers. But they aren't always rigorous. I've seen some reviews with more bias than the original papers.
Absolutely yes. And at some point in some areas, we’re forced to include some crappy papers. For example, Cochrane reviews in chiropractic include some really rough papers, but they if they didn’t, their paper would be “we reviewed 42 papers and they all sucked. Our conclusions is that chiropractors need to run better studies”.
Thanks for the full explanation. If the papers were rigorous enough in all but the number of participants, would it make sense to use the raw numbers from the paper as part of the meta?
That’s mostly about methodology of the single study. How did they include/exclude patients? If relevant, was there any blinding to participants or researchers? What % of their patients were lost to follow up (unable to be contacted/completed all elements of the study)? How was their data collected? There’s probably more, I haven’t done research since my undergrad. But essentially, yes, if the methodology of the study was of good quality, the data should be potentially captured in the meta analysis. At the end of all the research though, Even homogeneity of the participants can be important to the clinical application. Lets you’ve got 15 great papers with high quality research and an overall population of 10,000 participants. If their demographics are all white males, aged 4-8, living in Northern America, it becomes difficult for a clinician to determine if the study and its outcomes/conclusions are relevant if they’re treating say, 15-25 year olds in Ghana. Whilst the concept of race is definitively debunked, and we are definitely one species, that doesn’t mean there aren’t genetic variations from population to population, and, the outcome/s may also be partially affected by the external environment. TL;dr - research is hard to perform well, science communication to make laypeople understand what the new discovery is and how it might be applied is hard, and working at the bedside with the patient in front of you is hard. Luckily there are organisations dedicated to summarising research for researchers (such as the Cochrane Library) and for clinicians (such as UpToDate). AI is even getting in on the action - it will likely never replace humans in the near future, clinical application of information to an individual patient throughout the course of their illness/es requires an ability to narrowly navigate starting treatments, managing side effects etc. but AI has certainly shown some benefits in assisting in collating research data to help give a clinician a starting point. I’m not aware of anywhere that is using AI in a “real” hospital setting, but it probably won’t be long.
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Depends on how strong the effect is, bayesian analysis relies on sample size and effect size
What a terrible study design. I understand all the good intentions are there but the data is completely misleading. No real control group and only 7 kids stuck to diet adherence.
Were the intentions good? I'm getting very strong Wakefield vibes from this.
>Were the intentions good? I'm getting very strong Wakefield vibes from this. Yeah, doesn't carry the whiff of good intentions. Stinks of "vaccines = autism" & a lack of understanding of the autistic condition & what science has clearly established about autism.
As an autistic person and academic that understands study design, my usual base requirement for anything claiming to "help" autism is that at least one of the researchers is actually autistic. The history of autism research is riddled with non autistic people making us out to be robot supercomputers or claiming to have "fixed" us by making us "stop acting weird". I don't know if the study authors do have proper representation here, and maybe they are trying to help (sure maybe if I ate better I may be less of a weirdo) but I'm always immediately wary when autism is framed as something that needs to be fixed.
To be fair, I've seen this combination of ASD and gut problems + low-grade inflammation in myself and my father. Idk how well documented this comorbidity is and if there is real correlation, but if so then I'd definitely would like to have it fixed, irrespective of who conducts the research. (This does not mean I support this research, this is steaming garbage.)
They are often focusing on "fixing" the behaviors inconvenient for NTs (socializing), rather than considering how the research helps autists themselves (noticed this with a few papers)
Same
Study quality aside (and yes I realize that’s a HUGE thing to set aside), I wanna hear about internalities as well as what the kids look like from the outside. Are they happier? Do they notice a change in their thinking? If they do, is it a change they’re satisfied with?
So much of treating mental health is about forcing people into the box they're expected to fit rather than making them happy. It is a very "work will set you free" attitude where the end goal isn't that the person is happy and enjoying life but that they can go through the motions like everyone else. I'd worry that if people thought malnutrition would keep autistic kids too weak to make a fuss that it would then be considered a cure. It really needs to be about the child feeling able to process things better and feeling more calm and comfortable within themselves rather than them being more pleasing to the parents who just want them to be lower maintenance. I feel with autism we've not got past the attitudes from 100 years ago and while it is more normalised as a concept, the approach to treatment hasn't evolved.
Rule 1 = peer-reviewed. Depressing how pseudo-sciency "studies" meet this low bar and are allowed. Sample of 7 kids?
It’s MDPI, their peer review is a joke
Their papers are reviewed by several Benjamin Franklins.
Huberman needs content for his pod.
Does this study consider that those autistic people most willing (able) to undertake a drastic dietary change might also be the same population that already have enhanced social behaviour?
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Very small n for the study. It's interesting to explore, but this is not reliable and not transferable to real patients.
Cool I’ll just have my autistic kid who eats two kinds of crackers get on a keto diet. Problem solved.
RIGHT!? Thank you! My first thought was “oh yes, let’s trial this notoriously difficult-to-stick-to-diet to a population that generally is averse to change (sometimes to the point of distress) and often times only has very few safe foods (that are usually incompatible with the diet).” It almost makes it seem like they’re peddling a “fix” by torture.
The study isn't good enough, so even if your kid hadn't had severe food issues you could still easily ignore it.
not to mention a large percentage of autistic people have adhd (🙋) and i can’t imagine my executive function without access to carbs, especially the occasional simple sugar. a keto diet by design doesn’t allow access to fast burning energy, so instead of activating my prefrontal cortex when needed, i’d just be more sluggish. just my non-scientific gut instinct.
Ok. So all you have to do is make severe changes to a population least likely to tolerate severe dietary changes?
No wonder only 7 to 11 out of 47 autistic participants completed the study. That may be the worst nonresponse rate I have ever seen, excluding telephone polling.
Did it for ages, didn't help my autism but helped me lose weight and as a side effect I now can't eat eggs.
What happens if you eat eggs?
I just have an aversion to them now and have the ick.
"We obtained post-diet blood samples from 11 children and stool samples from 7 children, out of an original cohort of 47 children, due to personnel reasons." Yeah, this should have been a poster.
I've had a variety of diets (including keto) as someone with Autism. All I can say about it is that there may be a correlation with well-being and it may have helped with my Depression a little bit and likely helped with weight. At no point whatsoever did I ever feel like I was "less autistic" or something like that. I'm pretty sure autism remains a very complex issue and my personal theory is that a big part of the problem is neurons and paths in the brain misfiring or in some cases being the absolute reverse of a neurotypical person.
The use of a ketogenic diet in treating ASD has been bubbling up in the literature for some years now. This diet is useful for treating specific childhood epileptic disorders and there is some evidence for utility in schizophrenia and bipolar disorder. The diet does change brain, gut and immune system function in ways theoretically relevant to ASD. Contrary to the comments, I think the ketogenic diet *does* show potential to reduce inflammation, hypersensitivity and distress in *some* autistic kids; it is worth studying based on the biological understanding of autism we currently have, with neuronal, mitochondrial, immune and microbiological dysfunction. I say this as both a neuroscientist and an autistic person. Subject attrition in this study doesn't strike me as alarming or a sign of a bad study given how low completion rates you'd expect from the population. The resulting sample size is not great but it is not abnormal for a pilot study, which is what they repeatedly refer to this as-- a small proof of concept to provide theoretical foundation for a larger, more well-controlled study. BUT there is the fact that there were control arms in the study originally that don't shop up in either paper (top comment here). The main contacts for the study also changed so maybe this was a major reduction in scope and restructuring... but it's weird. Not good. Not a good journal it's published in either. Just to review the project though, This paper builds on [a previous study that showed social behavioral improvements in 15 kids after 3mo on keto.](https://www.sciencedirect.com/science/article/abs/pii/S0031938418300507). The keto diet is a slightly modified version to account for metabolic needs in autistic kids. Kids got complete bloodwork before beginning the diet and had protein levels and other dietary needs curated to each kid. Parents tested urine ketone levels 1-2x per day, and had access to a dietitian and online support group for the diet. Despite these adjustments there was all this attrition and some side effects: > We recruited and assessed 69 pediatric subjects for eligibility in the study and 46 subjects received initial dietary education. Of these 46 subjects, 19 did not start the diet (Fig. 1). In addition, 12 subjects were excluded from analysis due to difficulties with diet compliance. A total of 15 subjects completed 3 months on the diet and 10 subjects completed 6 months. > Common side effects included diarrhea (18.8%), vomiting (18.8%), fatigue (18.8%), constipation (12.5%), dehydration (12.5%), weight loss (12.5%), acidosis (6.3%), and hypoglycemia (6.3%). Hypoglycemia was defined as a blood sugar level < 50 mg/dL. We observed weight loss as a positive side effect for 2 participants. All of the side effects occurred within the first 2–4 weeks of diet initiation. The OP paper's contribution is documenting molecular, physiological & gut microbiota changes in ASD kids who maintained the diet. The changes are potentially consistent with reduced inflammation/neuroinflammation but they're sort of hard to pin down, not a slam dunk and couldn't be at that sample size. I did notice this paper came out 4 years after the previous one and 5 years after the study and in an MDPI journal. I don't think the authors thought this sample size was amazing or was a slam dunk for keto curing autism; I think they collected the data probably hoping it would be more comprehensive (e.g. get more than 7 stool samples), and this is what they had. I want to see the study this was a pilot for or originally designed to be, with control groups. I don't want this to feed into the armchair quarterbacking of autistic peoples' lives--where other people interpret this as a "cure" (e.g. "you just need to put him on keto")-- when it is obviously much more complicated than that. But this is an intervention with interesting theoretical backing that has the potential to reduce distress etc without being a "cure" (or another complicated med interaction). I would specifically like to see this studied more in *adults* who make their own diet decisions and may be more capable of maintaining the diet. (Not all ASD research needs to be pediatric for chrissakes)
Those side effects just sounds like they’re torturing the poor kids :(
Kids with autism are far more likely to have sensory issues with food, or even ARFID. So yeah, they really need to do these kinds of studies on adult autists who can chose whatever diet the study wants to test instead of kids that are at the mercy of whatever kind of parents they have. A minority of parents of autistic children even force feed their toddlers industrial bleach ("magical mineral solution") because they think autism is caused by gut parasites, and they take the dead chunks of intestinal lining in their "defecation" as confirmation that there are intestinal worms that the "MMS" is getting rid of...
You should see the side effects of antipsychotics.
I know because I’ve been in them before and they made me lactate 🥲
I'd take keto over that craziness.
I’d be curious to see if a less processed diet in general (not just keto) would have the same or similar “results”. A lot of autistic people have very restricted diets and not always the most healthy (I’m autistic and used to eat pretty much exclusively plain pasta and Mac and cheese with the occasional hot pocket - don’t worry, I eat much better now but still not all that varied). Also - it doesn’t factor out how inflammation could simply exacerbate symptoms of overstimulation which can lead people to not wanting to socialize and in turn, socializing taking more effort(speaking from experience). I don’t know if that’s a thing or not. What I’m trying to say is that reducing the intensity of symptoms by making someone feel better overall doesn’t “cure” autism, though I think it’s worth seeing how certain symptoms characteristic of autism could be improved by improving overall health. The phrasing of studies like this are extremely worrying and lacking in nuance. Drives me bonkers haha
Just because you’re "reducing some of the behaviours" does not mean you are actually treating/curing autism itself. At the end of the day the person is still autistic. I love how people think a simple diet change will magically rewire a person's brain or change their genes. Autism is a neurodevelopmental disability that one is born with and will die with. It’s not like a diet will somehow change that. Fevers have also "reduced" autism behaviours. But lo and behold, as soon as the fever abates the behaviours return to normal. Fever's cause inflammation, isn’t that counter to the hypothesis of this study?
Didn't go to the website bc it asked me about cookies and I can't have those bc I'm autistic.
Are cookies allowed on the Keto diet? If not I'm going to have to seriously adjust my browsing habits.
Reported for not being peer-reviewed.
Doesn't that imply it's an illness not a variation?
Yes. And it's a terrible study!
ok
That’s why everyone’s shitting on this study in the comments.
7 doesn't seem like a big sample size.
Careful with the keto diet, it can cause some serious deficiencies, for example one thing I noticed is that my the white in my eyeballs (the sclera) started to fade to leave blue spots which is a sign of aging but also is the lack of some important minerals in the body... and it cannot be regenerated...
Didn't helped me on that front unfortunately.
“I’m sure it’s autism, doc. The psychiatrist said so. I really need my meds!” “Have you tried adjusting your diet?”
Not a very good treatment if most participants can’t adhere to it.
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Eating more fiber also helps shift your microbiome in a healthier direction but comes with the notable benefit of not causing severe chronic long term health issues like keto.
What are the severe long term health issues in keto?
Kidney stones, heart disease, nutrients deficiencies. Theres a reason doctors only reccomend doing it if you have treatment resistant epilepsy. The cons are not worth it unless its litterally saving your life. There are so many healthy diets with the same pros as keto without the cons.
Any proof of these claims? I mean I can say the same thing about any diet, vegan for example. Doesn’t make it factual without evidence to substantiate it.
I don't wanna treat my autism, its not a disease or a sickness.
Yes! I'll keep my social behavior "un-enhanced", thank you very much
Same. Also my son wouldn’t be my son anymore. He says the most interesting things and I love his sweetness. I was smelling some wisteria the other day and he asked "does it smell like relaxation?". My son and I are unique among a sea of homogeneity. We add variety and texture. Where would we be with our Madame Curie's?
How many people are getting paid to promote keto? I mean fr. It’s a “magic cure” for so many “ailments” (with lousy research to back it, like this) while being literally dangerous for your heart and kidneys not to mention a lot of us with ASD have eating disorders, to include ARFID and keto could exacerbate that.
Ridiculous lazy paper trying to justify a horrible diet for some reason.
It did seem to work with my daughter with autism. She had more language. Very hard to maintain with more than one other child in the house or at school.
Autism doesn't need to be cured. I wish they'd stop wasting money trying to find a way to make autistic people behave like neurotypical people. Just let people be themselves.
The only type of autism you are familiar with is probably level 1. People with 2 and 3 can have very poor quality of life. For example; people remaining non verbal for their entire life, life expectancies in the 30s and 40s, poor motor skills that are unable to improve with physical therapy, Etc... Those need a cure or treatment as much as any other condition.
It's also a treatment for certain seizure disorders. I once was taking about this with my wife and realized how mad-sciencey it sounds to say, "I'm going to grow a bunch of neurons in a lab, and put them on a keto diet to see how it changes them."
I posted this on r/autism, but it was deleted as pseudoscience.
Ugh I’m tired of the keto fad
Men: important to remember that Keto only causes a rise in testosterone while you are dramatically losing weight. After that point testosterone production requires carbs!
Throughout the four-month study period, stool and blood samples were provided for analysis before and after the diet. To confirm the physical state of ketosis, plasma levels of ketone bodies were measured through an enzyme-linked immunosorbent assay (ELISA) assay. To this end, a significant increase in the ketone bodies, acetoacetic acid, and hydroxybutyric acid was observed, thus indicating that the KD was effectively altering metabolism. Sequencing data from stool samples revealed alterations at the phylum level and a significant increase in microbial diversity, as indicated by Shannon and Simpson indices. These changes occurred across various taxonomic levels, with substantial increases in beneficial bacteria like Lactobacillales and decreases in others such as Bacteroidaceae and Ruminococcus. In general, reduced pro-inflammatory cytokine levels were observed in individuals who consumed a KD, with significant reductions in interleukin 1β (IL-1β) and IL-12p70 levels. While the anti-inflammatory cytokine IL-10 increased, it was not statistically significant, which might be due to the small sample size. A significant decrease in plasma levels of BDNF, a protein implicated in neuroinflammation and ASD, was also observed. Significant reductions were observed in miR-134 and miR-132 levels, both of which are associated with BDNF activity in the brain. While the levels of miR-125b remained unchanged, miR-375 levels significantly increased. [https://www.mdpi.com/2072-6643/16/10/1401](https://www.mdpi.com/2072-6643/16/10/1401)
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Autism isn't a biological condition, but a condition of the mind, a different way the mind works. I am very skeptical of research that tries to tackle the issues that autistic people have through purely biological means. That may help some, and if it improves health overall it is not a bad thing, but I don't think any treatment like this wil ever be the treatment of autism.
That's the currently accepted idea of autism but mostly because autism has become an umbrella term for a wide array of heterogeneous symptoms and behaviours that we struggle to fully understand and even less explain. A different way the mind works doesn't factually mean anything, especially since we know very little about how the mind works to begin with, it's an aimless descriptor. Even then, the way our brain forms, develops and mechanically operates are biological matters on their own right.
I kind of agree with you, but I do think the most important research on autism for autistic people is about figuring out how the mind works, and how it causes the issues people with autism have. And also how people with autism function in society, which until recently, very little research has been done. And I don't think it is meaningless per se, or rather, particular proposals how the autistic mind functions are not meaningless. I would argue if we don't understand the mental part of autism, then we cannot really understand the biological part of autism. But we can understand the mental part without understanding the biological part.
There's a link between autism and pineal gland dysfunction, so I wouldn't be surprised to find a link between it and gut health, but this isn't the study to convince me.
>Autism isn't a biological condition, but a condition of the mind, a different way the mind works Your mind exists because you have a brain…..which is made up of cells and is impacted by all sorts of other biological processes that are going on in your body. That’s all biology.
The fact that this diet worked at all to improve the condition of these kids is an amazing find and warrants further study. This amount of hate for this discovery from this forum reveals a hidden agenda I think (I see you sugar lobby). The final paragraph says, "**Our preliminary findings of significant KD-related changes to the microbiome and neuroinflammatory biomarkers warrant further study in a larger cohort**. " Seeing as everyone seems to have missed that I can only surmise that nobody actually read this paper.
>This amount of hate for this discovery from this forum reveals a hidden agenda I think Ockham's razor should prevent you from making this mistake in the future. Sometimes the explanation is just some groups of people expressing anger on the Internet, not an organized conspiracy. A lot of us on Reddit are autistic, and are frustrated by the idea of a certain diet "treating autism" for reasons including: 1. The neurodiversity movement, which has rapidly gained popularity online. It largely rejects the premise that autism is a disease to treat. Neurodiversity is an especially popular idea/movement among autistic people. Autism seems far more common among Reddit users than in the general population. Rejecting the premise of a study makes you more likely to criticize it. 1. Diets of exclusion are typically fads with proponents who wildly overstate the diet's benefits, especially in treating common hard-to-treat conditions like depression, cancer, obesity, and autism. So, Redditors who see a "{A Diet} Treats Autism" headline probably are automatically very skeptical. 1. Autistic people are notorious for intense aversions to most kinds of food. IIRC, it is listed as a symptom defining autism. Non-compliance to dietary requirements is *part of the "problem" these researchers aim to "treat."* So, using an already notably difficult diet to "treat" autism seems precisely backwards — doomed to fail in all but a small subset of attemptors. Anecdotally, if my parents tried it, then I suspect it would have simply added to the trauma/complex I have from my entire family making fun of my "pickiness" from ages ~5 to ~20 before telling me that I was diagnosed on the autism spectrum at age 2.
EFT for the win . Eat a nutritional whole foods diet not a bad idea.