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Comment by lambdaba | Hacker News Reader

I just found out about Thiamine (vitamin B1) megadose therapy for Parkinson's:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762356/

Another study: https://pubmed.ncbi.nlm.nih.gov/26505466/

> Conclusions: Administration of parenteral high-dose thiamine was effective in reversing PD motor and nonmotor symptoms. The clinical improvement was stable over time in all the patients. From our clinical evidence, we hypothesize that a dysfunction of thiamine-dependent metabolic processes could cause selective neural damage in the centers typically affected by this disease and might be a fundamental molecular event provoking neurodegeneration. Thiamine could have both restorative and neuroprotective action in PD.

This experience report of halting Parkinson's: https://youtu.be/iuSOQOTyB9w

View on HN

https://www.michaeljfox.org/news/thiamine-vitamin-b1-and-par...

The Michael J Fox foundation is more muted and says evidence is still missing. There have only been 2 trials and both were missing a placebo control group.

It's for the US and Canada only.

Imagine having Parkinsons and being in the placebo control group.

Today we should assume that it's harmless to get the placebo.

Only if a trial shows extraordinary consistent benefit without drawbacks would they stop it because the placebo group is harmed for lack of access to the treatment.

I used to share this sentiment for Parkinsons and other currently-intractable conditions. I still do sometimes, depending on the circumstances of the patient in question.

But the thing that stopped me generalising this was seeing second-hand that trialing a new treatment can be extraordinarily dangerous (and/or fatal).

Imagine being in the experiment group and the untested treatment being a catastrophic failure.

Imagine symptoms improving being in the placebo group?

What are the statistics on that?

Being part of a rigorous process by which a cure may be found? Sign me up.

You're thinking that even a gamble on untested / unverified treatment might improve their lives; it might, but it might also do nothing, make it work, or worst case kill them.

But I get it. My partner has an untreatable condition (like EDS, but without the genetic markers); they'd jump on any kind of hope, even experimental at this point.

If a treatment in a placebo controlled study shows a vast improvement over placebo, the studies are sometimes finished early and are considered 'unethical to continue'.

e.g. HAART for HIV/AIDS.

> 100 mg of thiamine administered intramuscularly twice a week

Is it possible to get anywhere near this much with dietary thiamine?

> Is it possible to get anywhere near this much with dietary thiamine?

High thiamine food stuffs have a few milligram at most so it would take some effort. However, many B1 vitamin tablets have 100mg-300mg, although I wonder how well that is absorbed compared with an intramuscular shot - it would seem that you could consume the equivalent of 200mg a week.

I read somewhere that gut can only let around 80mg thiamine/day and gut gets saturated over time, so only IM/IV would work long-term.

If this Was discovered 10 years ago, I’m assuming it must be fairly limited in helping, or the results haven’t lasted or something?

The cynic in me assumes that it's because this is not a patentable drug.

EDIT:

MJF foundation is aware of it at least - https://www.michaeljfox.org/news/thiamine-vitamin-b1-and-par..., but points out problems with the study. Further Googling quickly leads to the usual quackery about the magical properties of different supplements and vitamins. Hope this goes somewhere though.

No way. About five years ago there was a quack-y study about reducing death in sepsis which called for high-dose vitamin C, thiamine and steroids. None of these are patent protected. The first study purported to show a 100% reduction in mortality. There were many RCTs done after this which did not bear out the effect, and it has now essentially been proven to be ineffective. it is possible to fund studies without industry money.

Who actually thought that steroids help with an infection? Don't those usually make you more susceptible?

During COVID, steroids were rapidly identified as providing a positive survival benefit and became standard of care.

There is actually a good reason to think that steroids are beneficial in severe infections. This is because often in a severe infection/inflammation, a big portion of the damage is done by the inflammatory response.

Reading about the pathophysiology of influenza 13 years ago after H1N1, I came to this conclusion, and it was trialed, but good quality studies showed it to not be effective.

COVID has a slightly different pathophysiology and in COVID it works.

But yea, as a rule, it’s not a good idea to dose with steroids if sick

If most of the actual harm is being done by your immune system going into overdrive, then yeah, steroids can help. You'd want to simultaneously treat the infection, of course.

"Multiple randomized trials indicate that systemic corticosteroid therapy improves clinical outcomes and reduces mortality in hospitalized patients with COVID-19 who require supplemental oxygen, presumably by mitigating the COVID-19-induced systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction."

https://www.covid19treatmentguidelines.nih.gov/therapies/imm...

But yes, you're also right that it usually makes you more susceptible to infection because your immune system isn't working as hard.

I can see that in some cases. I doubt that would be beneficial in the case of sepsis, right?

Actually, it's complicated, and there really isn't consensus one way or another.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949415/

"Seventeen meta-analyses of these studies have been performed and have similarly shown conflicting results with some demonstrating a survival advantage (4-6) while other have not (7-10). Consequently, true equipoise exists with regards to the clinical benefit of corticosteroids in patients with severe sepsis and septic shock.

...

In summary, the use of corticosteroids in patients with severe sepsis and septic shock is not associated with improved patient centered outcomes, however this treatment is safe and without an increased risk of complications. Corticosteroids appear to have synergistic biological effects when combined with intravenous vitamin C and thiamine and may be associated with improved patient centered outcomes (21)."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604467/

"In this review article, we reviewed a total of eight different articles being done in last 10 years, relevant to the clinical outcome and eﬀects of corticosteroids. Among those, two demonstrated improved clinical outcomes, two showed both improved clinical outcomes and decreased mortality, three showed increased adverse eﬀects, and the remaining one showed unequivocal results."

Interesting

Chronically, yes. Sometimes they can help address a more serious acute issue.

I've taken steroids when I had a virus because the symptoms caused by the virus were severe. The doctor made it clear that I should take it as little as possible, but it was "your throat is going to close up OR it takes a little longer to get better".

There is a fair amount of research on diet and nutrition. Much of that is not patentable. For example, I think a recent one was all over the news about magnesium rich foods lowering risk for dementia. Unfortunately this area sees a lot of back and forth in some areas (like with eggs).

This is such a horseshit characterisation of medical research.

Everyone bangs in about the medical industrial complex, and points to either herbs and vitamins, or more recently ivermectin, or hydroxychloroquine.

Everyone conveniently just rolls over the fact that steroids (also patent free) were rapidly identified by a massive research study in the UK, became standard of care, and saved hundreds of thousands of lives.

Is the pharma industry broken? Yes. Are there doctors who are conveniently leaving the cheap things on the shelf so a pharma company can profit off misery? Doctors are people too. In the most extreme form of this conspiracy thinking, apparently no doctors get or die from cancer. Just think on that for a second

Most doctors would laugh at vitamin supplementation even at pharmaceutic megadoses despite people reporting they feel much better. I have seen both GPs and a neurosurgeon laughing about it.

When in doubt, just throw the kitchen sink at the problem.

https://www.hangoverkw.com/

Is it because of thiamine dysfunction or because thiamine at 2000x RDA doses acts as a carbonic anhydrase inhibitor, i.e. would acetazolamide work the same?

This further assures my thought that Parkinsons is caused by gut bacteria

Say more about your theory

A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

https://elifesciences.org/articles/53111

Note, this was in mono-colonized gnotobiotic mice.

Published in the "Journal of Integrative and Complementary Medicine", "The leading peer-reviewed journal providing scientific research for the evaluation and integration of complementary medicine into mainstream medical practice."

"Integrative and Complementary Medicine" is a fancy way of saying quackery.

Also, the video you linked to is on a channel run by a person describing himself as "a certified functional medicine practitioner & naturopathic nutritional therapist [..]. He enjoys making videos on a wide variety of health-related topics ranging from nutritional biochemistry to circadian biology, animal-based nutrition, and the dangers of electromagnetic radiation."

No further questions, your honor.

My pet peeve is people dismissing potentially very valuable scientific results because they’re afraid of quackery…

Yes we should be cautious but no we should not dismiss. In fact I consider myself very fortunate for stumbling on this information as it may be very helpful for someone I love and I want to explore every possible way that can help.

That's the precise essence of why quackery is dangerous. People are searching for "every possible way that can help" and quackery can easily exploit that natural tendency. (I am not qualified to render any opinion on whether this specific protocol is quackery.)

That's also the precise essence of throwing out the baby with the bathwater.

I'd much rather have the information in front of me so I can evaluate it and make my own determinations. If the parent commenter had their way I would've never seen this information. Now I can actually vet it out and do my own research.

I think it's infinitely more dangerous to deprive people of information.

> much rather have the information in front of me so I can evaluate it and make my own determinations

This is the danger. Most people, myself included, are not qualified to make that determination alone. In this case, as expected, it looks like it was crap [1][2].

I'm not arguing in any way for censoring anything. But there is legitimate danger when people, often desperate, compare legitimate medical research, which will be subdued, with quackery, which will be ostentatious, and then, worst case, reject the actual medicine or hurt themselves trying to administer rogue therapies.

[1] https://news.ycombinator.com/item?id=35771376

[2] https://news.ycombinator.com/item?id=35771048

One notable exception to that is Kyrie Irving and other Covid vaccine skeptics, who were amazingly somehow able to "do their own research"

Counterpoint. Historically people have not been able to evaluate these types of claims. See the history of snake oil salesmen and the origins of the Food Drug and Cosmetics Act.

I don’t think it is a problem when people look at stuff, think it is interesting and try something relatively benign on themselves. For me the problem is when people start trying to play doctor without medical training or license.

I agree with you in regards to the dangers of snake oil and snake oil salesmen and the general inability for the vast majority of people to properly vet medical information.

That being said, I would say it’s unfortunately by necessity that people start trying to play doctor. I live in Canada, our healthcare system is currently in shambles such that it’s impossible to get timely care. Even the care we do get is time-limited and only focused on saving your life (which is great, but ignores the value of improving quality of life too). Also most of our medical interventions are so far behind the state of the art due to a Byzantine regulatory process that anyone actually trying to help a loved one with a health issue is forced to take matters into their own hands otherwise we fall through the cracks. The medical system is simply failing way too many people in Canada that it’s inevitable people Will take their health and the health of their loved ones into their own hands by necessity.

The problem is the lack of incentives to take the “huh that’s interesting, but I don’t know if I can trust it because it’s published in a quack journal” … and ever reproduce the research and get it into more trusted more prestigious journals.

There’s a reproducibility crisis in many fields of research, and medical research has multiple confounding factors, the “no prestige in just redoing the research”, lack of money for trying things that might fail to generate RoI for pharmaceutical companies, and the general medical research problems of clinical trails and ethics review and all the other stuff involved in good quality medical research.

Consequently this stuff gets thrown in the quackery bucket and ignored. It’s frustrating to see things that won’t hurt anyone to try again and properly debunk or expand the evidence for, winding up in an ideological trench war where the outcome is getting to enter round two of the “funding your actual research” trench war.

If you had a legitimate research finding, why would you publish it in a quack journal?

Presumably, because the more prestigious journals declined to publish it.

Why did all of them decline to publish it? There was probably a reason. A paper being published in a quack journal does actually carry a signal about the quality of paper, IMO. No one turns down publishing in Cell or Neuron to publish in Donald's Journal o' Quackery and Crockpot Recipes.

Yes, the point you’re making is valid and I generally speaking agree with it. The issue isn’t necessarily that it was published in a quack journal, it’s that now this idea has been published in a quack journal it’s “tainted” and suggesting that it be looked at again for any other reason than some significant new evidence discovered completely by accident (because you’re a quack too if you believed the idea in this paper) and it has to be pretty significant evidence too (otherwise it might look like you are cherry picking evidence for your quack belief) and only then can you consider the idea worth properly studying… all because by originally being published in a quack journal, the idea has the taint of quackery.

Now most quack research is not particularly useful… but it can be made more useful to society if it’s used properly, we should be more willing to publish reproductions and failures to reproduce existing research, and we should be encouraging early career scientists in all disciplines to take this kind of quack research and to prove it wrong, it’s all there to disprove, easy done. We would get more critical thinking in our research students we would get more evidence to disprove other quack research and every now and then we might even stumble onto something good that would have gone ignored as just quackery for an unknown period of time.

If we want to fix the reproduction crisis we can’t ignore the shit research papers and only reproduce the good ones we think might work, we need to be willing to look at research like this, which involves a pretty/relatively harmless high dose vitamin regimen that can be easily monitored by a clinician performing the research work (double blinds of course) and then we go from “idea that won’t be touched again and quacks try to convince people with flimsy research” to “idea conclusively proven or disproven and scientifically have settled the question without leaving reasonable doubts that can be used by quackery peddlers or others mis-using the scientific method for their own gain.

This isn't an unfounded fear of quackery, they've supported their view to an extent.

You did not, in fact, stumble upon information. You stumbled on a person making statements. There’s a difference, especially when lives are at stake.

In this context they're functionally equivalent, in that anyone making statements is also communicating information. Could you explain the difference that I did not grasp?

Do explore it, but check other (reputable) sources for the effect on Parkinson and for counter-indications (although there don't seem to be obvious ones).

The journal, however, is bad. Looking for articles, the first I found claims that sounds of nature have a positive effect on gambling addicts, something unwarranted by the actual experimental conditions. The peer review and editorial process seem to be lacking.

I mean sounds of nature have a positive effect on most people so that sounds like low hanging fruit, lol.

Agreed; this is akin to the "woo" applied writ large to the lucid dreaming phenomenology; or anything "metaphysical" crossing into "empirical" -- I have a fondness for the UAP topic and it's poster child for this effect. I know there's a grain of truth in the bucket but the wackery is beyond my ability to dredge.

It's not fear, it's challenging a conclusion made by people based on their credentials. If the science stands up to scrutiny and peer review, then great, but if it doesn't then it's not true.

The quackery label comes in not from the science but from the people behind it and the monikers / titles that they applied to themselves - unrecognized and not formally tested monikers / titles.

The formal testing is so that there's a proven and traceable minimum knowledge and background behind a person's statements. Like a bachelor's degree for a software engineer vs a two week boot camp.

Reminds me of this post I saw on CompSci Reddit once. A person claimed to have made an O(n) algorithm for finding loops in a graph (or something like that), and he posted the source code. The comments were all in the line "big if true, but I'm going to have to see a peer reviewed paper" to which he answered along the lines of: "I'm paid to write code, I'm not paid to write papers. I made this algorithm solve a problem at work, take it or leave it".

The thread died without anyone actually checking if his algorithm worked or not.

Who knows...

You know what you're right. But not far behind these quacks are neurologists.

If you've ever had someone in your family that might have had Alzheimers or Parkinsons you'll know what I mean.

I think that is being unfair. It's the sad reality that for many neurological conditions we don't have good treatments or cures. However, things like levodopa are godsends for many with Parkinsons, for example.

God bless you for sharing this. Thank you.

Take a look at zinc instead. It helps increase the activity of enzymes that break down alpha-synuclein.

https://academic.oup.com/hmg/article/23/11/2791/621896

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