Hyperbaric oxygen therapy reverses hallmarks of Alzheimer’s disease and dementia
technology.org
technology.org
6 subjects!? Did anyone actually check the study they registered? https://clinicaltrials.gov/ct2/show/NCT02790541
Their actual clinical trial had 62 subjects and it had a control arm. The paper has only 6 subjects and no controls.
If I run an experiment with 60 people, I can find evidence for anything (precognition, telekinesis, etc.) if I'm allowed to cherry pick 6 data points and drop any controls.
The authors should be ashamed for polluting the scientific record with this junk.
If it was preregistered perhaps the journal were obligated to publish the results no matter the outcome. Some journals do this ostensibly to combat publication bias.
I didn’t read the whole thing: are the authors actually claiming the human data are informative? If so, that is wrong. But if they are just saying “hey, these are the data!” I wouldn’t be so harsh.
Edit: Just read the methods. Data collection was 2016 to 2020, so COVID probably wasn’t the issue. They were selected for poor memory yet normal cognition in other domains, so it is possible they couldn’t recruit the number of subjects they proposed who met this criteria and also were willing and able to complete the treatment.
I’m now quite confident the memory result is regression to the mean, and therefore nothing to do with the treatment.
I also read the portion of the discussion related to cognition. They are claiming to have found something meaningful (in the human data) when they definitely haven’t.
This is why we analyse on an intention-to-treat basis rather than who actually received the treatment. The publication makes no such attempt to explain this potential source of bias.
I'm not being harsh. This is basic due diligence that the editors and reviewers at Aging must do, by their own rules.
Aging agreed to follow the ICMJE (International Committee of Medical Journal Editors) rules (for many reasons including pressure from funding agencies). Those rules are fairly extensive. Among them is that you register your trial, then after you're done you must complete your trial and update it. The ICMJE rules literally say "The purpose of clinical trial registration is to prevent selective publication and selective reporting of research outcomes"
The 62 patients aren't theoretical. They actually existed and were enrolled in the trial. That's why the preregistration says
> Actual Enrollment : 62 participants
Before the authors completed the trial it would have said "Anticipated Enrollment". They had to update this field to be able to publish according to the ICMJE.
So this data exists. What happened to it?
Did the authors cherry pick? Then they could show that God exists.
Did the authors exclude subjects because they died, declined too much, developed diabetes, etc? Then that completely biases their results. They need to carefully explain what happened. They need to correct for this source of bias in all of their statistics and can't just publish whatever they want and pretend the study as registered didn't exist.
This wasn't a mistake either. If you look at the data sharing section they said they're undecided if they will give you the raw data to check their results. I wonder why?
But it gets worse. This violates a whole list of Aging's rules. https://www.aging-us.com/for-authors
> Aging supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration. All trials initiated after 1 July 2005 must be registered prospectively in a publicly accessible registry (i.e., before patient recruitment has begun), or they will not be considered for publication. Authors of randomized controlled trials must adhere to the CONSORT reporting guidelines appropriate to their trial design. Please check the CONSORT statement Web site for information on the appropriate guidelines for specific trial types. Before the paper can enter peer review authors must: 1) name in the paper trial registry, trial registration number, and IRB and 2) provide a copy of the trial protocol and a completed CONSORT checklist as supporting files. The CONSORT flow diagram must be included as Figure 1. Any deviation from the trial protocol must be explained in the paper. Authors must explicitly discuss informed consent in their paper, and AGING reserves the right to ask for a copy of the patient consent form. Information on statistical methods or participants beyond what is indicated in the CONSORT statement should be reported in the Methods section.
Where's the CONSORT checklist? Where's the CONSORT flow diagram? "Any deviation from the trial protocol must be explained in the paper"
Let's look at another random paper from the same edition of Aging. "Association between tooth loss rate and risk of mild cognitive impairment in older adults: a population-based longitudinal study". https://www.aging-us.com/article/203504/pdf Figure 1 is the CONSORT flow diagram as required by Aging's own rules.
This is a boondoggle that doesn't even meet the most basic criteria for scientific publications.
So it looks like they cherry-picked the 6 subjects who did (by chance) worse on the memory task than the other tasks. Then regression to the mean happened, and voila! Some positive results.
The authors should be happy to have added to ongoing alzheimers research. Their actual claims are much less bold than the article makes them out to be.
Direct quotes from the paper:
> Motivated by these findings, we exposed elderly patients with significant memory loss at baseline to HBOT and observed an increase in CBF and improvement in cognitive performances. This study demonstrates HBOT efficacy in hypoxia-related neurological conditions, particularly in AD and aging.
> In summary, we showed here that HBOT offers multi-faceted neuroprotective effects on the complex pathology of Alzheimer’s disease and also improves CBF and cognition in humans.
> Given that HBOT is considered a safe and tolerable treatment currently being used in the clinic, the increasing number of clinical trials showing that HBOT improves cognitive function in patients suffering from chronic brain damage, the pre-clinical studies elucidating mechanisms of HBOT action, and the fact that there is presently no effective intervention for AD, HBOT should be considered as a therapeutic approach to slow the progression or even improve the pathophysiology responsible for this disease.
I can't imagine bolder claims than "we showed here that HBOT ... improves CBF and cognition in humans" and "HBOT should be considered as a therapeutic approach".
I mean this literally. I can't imagine it. What else could they have said that would be more direct aside from HBOT will cure you 100% guaranteed?
> The study population comprised adults (5 males, 1 female) with significant memory decline aged 64 years and older
> The protocol consisted of 60 daily sessions at 5 sessions per week within a three-month period. Each session included breathing 100% oxygen by mask at 2ATA for 90 min with 5 min air breaks every 20 min.
> At baseline, patients attained a mean global cognitive score (102.4±7.3) similar to the average score in the general population normalized for age and education level (100), while memory scores were significantly lower (86.6 ± 9.2). Cognitive assessment following HBOT revealed a significant increase in the global cognitive score (102.4 ± 7.3 to 109.5 ± 5.8, p=0.004), where memory, attention and information processing speed domain scores were the most ameliorated (Figure 8C). Moreover, post-HBOT mean memory scores improved to the mean score (100.9 ± 7.8), normalized per age and education level (100).
If this is a significant treatment of Alzheimer's then that's a breakthrough to me, what bar would you set?
Wouldn't having some kind of proof against a placebo or at least a dose-dependent improvement be the least possible requirements to actually believe the paper found any kind of effect at all?
If you randomly give 6 Alzheimer's patients an apple a day for 5 weeks, they could show improvements in cognitive tests by pure accident, especially for a disease that is known to ebb and flow.
> The peer review process employed by the journal has been criticized by Jeffrey Beall, a university librarian and expert on predatory open access publishing, who also included the journal and its publisher on his list of "potential, possible, or probable predatory scholarly open-access journals" in July 2015.
1. There is no control group. Since people get better with cognitive tests with practice, we don’t know whether these improvements were due to the treatment or just the normal practice effect. (Though if I were a betting person, my money is on the latter.)
2. Cognitive tests are not noiseless. The same person may vary by a few points between repeated tests. The modest improvements on most tests found here might not be above this noise floor.
3. The most impressive result (memory) is almost certainly regression to the mean. That is, the group did unusually poorly on this task in the first session by chance, then they performed more typically in the second, which looks falsely like a big improvement.
Basically, I think this paper provides no meaningful evidence of cognitive improvement in humans. I can’t speak about the mice stuff, that might be fine.
I'm a little surprised they wouldn't have done a larger secondary trial before publishing, the impact would have been much greater if the effect was still observed in a larger group, even if they still did not have a control group- or perhaps had an alternative treatment schedule (shorter exposure times- is treatment duration correlated with degree of improvement? Then you have less of a moral dilemma of denying participants of a useful treatment while still getting some data that would indicate the treatment itself actually does something).
(working on a PhD in genetics)
Resource constraints are a much more plausible explanation - running the study with a control group would cost twice as much (in time as well as money). This is either a pilot to apply for funding to run a better-controlled trial, or it's just not scientifically serious. Both are very plausible, in my experience.
I do feel confident in saying that Scientifically, the human data in this study are largely uninformative.
Edit: One way to think about this is assuming the effects are random and symmetric then the probability of going up is 1/2. If all 6 participants had increased scores, then the p-value is at least 1/2^6 and this is not taking into account the magnitude of the shift.
Should be called "collected case studies" or something.
106 is well within a standard deviation of both of those. In fact, 109.5 is only one standard deviation away from the first, and the reverse is almost true. How do they get p = 0.004?
I'm currently using it to treat long covid brain fog, out of interest, what are these reasons?
It's the first time in a year I can think clearly. Anyone with long covid should seriously look into this as a treatment, it has some solid science behind it and is very safe, albeit expensive.
At this point I've tried 14 different drugs, not a single thing has moved the needle except this.
More info here on it for long covid: https://oxygenhealing.co.uk/covid-19-hbot/post-covid-trials/
"The ata unit is used in place of atm to indicate the total pressure of the system, compared to a vacuum. For example, underwater pressure of 3 ata would mean that this pressure includes 1 atm of air pressure and thus 2 atm due to the water.", from https://en.wikipedia.org/wiki/Standard_atmosphere_(unit)#Pre...
One of the causes of my symptoms will be straight up organ damage, and there's plenty of evidence HBOT speeds up the healing of tissue damage. So any progress in this area should be permanent.
My dad was involved in MS research in the 80s utilizing hyperbaric oxygen. After some hopeful results, no clear evidence was found.
Seems like this is a great thing, hopefully it pans out over larger populations of patients.
There will also be some pulmonary oxygen toxicity effects. Based on the protocol described those will be limited and resolve quickly in most patients.
The oxygen exposure is too limited to cause any significant risk of neurological effects, like a seizure.
So I don't know whether this treatment is actually effective but it's not particularly dangerous.
Out of curiosity, what would this include? Smartphones? Bluetooth headphones (to be used with smartphones that are outside)? Smartwatches?
https://www.advocatehealth.com/assets/documents/subsites/lut...
We see several stories a year discussing the links between air pollution and dementia, and also a link between more exercise and less dementia. so it makes some sense to me that there might be a link between decreasing lung function and increasing dementia. if the function of the HBOT is to increase the ability of lungs to oxygenate blood, maybe there is a subtle but important threshold of blood oxygenation that we don't understand well enough.
note: I am not a medical professional at all, it just seems like there is a "lung function" commonality in several of these stories.
https://www.nytimes.com/2019/05/06/health/conference-room-ai...
Nitrogen is regular air is an anaesthetic. It literally makes you stupid, and the effects increase with pressure. If you want to be smarter you need to replace the nitrogen with helium. The high pitched voices are going to make Zoom meetings hilarious.
So generally working under pressure is totally impractical.
1. Isn’t hyperbaric therapy used by athletes to reduce inflammation?
2. Isn’t the failure of the amyloid hypothesis leading to researchers considering whether inflammation is the progenitor of Alzheimer’s?
So if hyperbaric therapy does work… could that be a sign in favor of the inflammation hypothesis? Although, the authors suggest the results are due to improved oxygenation rather than any anti-inflammatory effects.
Also, I’m not a doctor nor am I educated in medical things.
> Alzheimer's disease is believed to occur when abnormal amounts of amyloid beta, accumulating extracellularly as amyloid plaques, and tau proteins, accumulating intracellularly as neurofibrillary tangles, form in the brain affecting neuronal functioning and connectivity, resulting in a progressive loss of brain function.
Furthermore, 60% people over 80 have these plaques but only 10% develop dementia [3].
Ergo, the hypothesis that plaques cause of Alzheimer's is pretty much falsified. More than likely they may be a biomarker of some kind that may be associated with cognitive decline of some sort.
[1] https://pubmed.ncbi.nlm.nih.gov/30273552/
[2] https://www.advisory.com/daily-briefing/2020/02/12/alzheimer...
[3] https://nutritionreview.org/2021/07/amyloid-plaques-are-cons...
Your second link says this:
> researchers have said experimental treatments targeting the beta amyloid protein might not have worked in the past because the doses were too low or the patient populations used for the trials should have been younger
Again, that doesn't seem to be concluding the amyloid & tau street is a dead end.
The Alzheimer's Association site (alz.org) agrees:
> Alzheimer's has no cure, but one treatment — aducanumab (Aduhelm™) — is the first therapy to demonstrate that removing amyloid, one of the hallmarks of Alzheimer’s disease, from the brain is reasonably likely to reduce cognitive and functional decline in people living with early Alzheimer’s.
Check sci-hub: https://sci-hub.hkvisa.net/10.1016/j.bcp.2018.09.027
Quote:
> Furthermore, the blind adherence to the “Amyloid code” [297] has resulted in the overwhelming rationalization of clinical trial failures - the lack of validation of the amyloid hypothesis – as being due to recurring issues in their planning and execution, not that the hypothesis has failed in its validation. This viewpoint, described as “sheer obstinacy in the face of compelling proof ..[of being]… on the wrong track” [285] has also compromised the translational approach to AD therapeutics making the criteria for compound advancement from preclinical research to the clinic exclusively based on either a blind faith in a hypothesis or animal models that have proven irrelevant.
This addresses the special pleading you quoted from people who continue trying to explain away the failures of the amyloid model.
The writing is on the wall, but as they say, "science advances one funeral at a time".
Now let me be clear, I’m not a cheerleader for any of them. I have read every original paper on the pathophysiology of AD from the 60s through to 2014 and I saw in detail the debate bounce back and forth from Amyloid to Tau with sprinkles of ‘Type 3 diabetes’ and inflammation and back again like a game of tennis. The science will come out the way it will come out.
But there is nothing about our ability to remove plaques with no change in the disease that says that amyloid plaques don’t have a role in disease pathogenesis. Could be the damage is done and clearing them is irrelevant. We just don’t know enough
Hyperbaric oxygen therapy appears to be somewhat effective for accelerating healing certain soft tissue injuries. So athletes have used it. But it's not clear whether that therapy is any more effective than other recovery modalities. Research has been limited.
Some of us do go deeper and use mixed gasses with more oxygen, but we carefully limit oxygen exposure to ensure safety. Acute oxygen toxicity can cause a seizure which is usually fatal underwater. So we never go above 1.6 on the oxygen, and then only for brief periods.
They have been shown to significantly help with cognitive decline.
I mean "Ivermectin has been shown to significantly help with Covid" has the same weight to it, and I'd never recommend anyone take horse dewormer. Maybe if they had worms and it was the only thing available.
[0] https://www.merck.com/news/merck-statement-on-ivermectin-use...
It's a pity that the whole issue has become politicized, but that's modern times for you. That's why ivermectin is called 'horse dewormer' rather than simply a medicine for parasite infections with a number of human applications. It's a term like 'XXXX denier' which is used to tie a political adversary to concentration camps by playing on our disgust or fears.
Does it do anything for COVID? Dunno. Should it be a discussable matter without internet censorship and crazy people twitterstorms? Maybe. Am I sick of being propagandized by everyone? Yes.
https://www.nih.gov/research-training/medical-research-initi...
You might also want to let these researchers know that you disagree with their results
Eh? Lions Mane doesn't have any psychedelic or psychoactive effects.
In my last comment I was speaking from experience too - I tried taking it for 3 months, and never noticed any effects whatsoever.
(standard disclaimer - not using/promoting Ivermectin, just not a fan of media distortion)
“ The evidence so far has shown that H. erinaceus mycelium enriched with its active compounds is capable of delaying neuronal cell death in rats with neurodegenerative diseases, such as ischemic stroke, Parkinson's disease, Alzheimer's disease, and depression. Moreover, results have indicated that administration of H. erinaceus mycelia enriched with its active compounds can promote functional recovery and enhance nerve regeneration in rats with neuropathic pain or presbycusis. Despite that more clinical research is needed to fully understand the potential applications of erinacine-enriched Hericium erinaceus mycelium, the majority of preclinical data strongly suggests that it is safe and offers much-needed neuroprotective applications.”
Source: Neurohealth Properties of Hericium erinaceus Mycelia Enriched with Erinacines