[armchairdweller]

I went deep down the Pauling Vitamin C rabbit hole once and got to point out that many studies not seeing effects are not actually giving people gram-megadoses, but mg-homeopathic ones. This story might not be as closed as some podcasters and other influencers pretend. Maybe it’s not double nobel laureate Pauling who was so wrong that he has pretty much become a quack in popular knowledge, but the fields of nutrition and perhaps medical science that are shoddy.

In fact nutrition and medical science are quite well known to be some of the worst offenders when it comes to bad methods and scientific misconduct, particularly in the past few decades (as also shown by OPs link).

Also - like apparently many of those perpetuating the story - I got my initial opinion about the Vitamin C topic being quackery from Wikipedia, but know better now not to generally trust it for medical topics since it’s quite well known that marketing departments of the pharmaceutical industry have a lot of time on their hands to write articles that benefit them. I personally burned myself with a safe&effective&local medical product promoted there with scientifically sounding terms with all criticism erased or “debunked” around 2014 and have permanent eye damage now (there has been a class action lawsuit few years later).

But to add to the nobel-laureate-turned-venturous trope, here is a recent example from physics: https://en.wikipedia.org/wiki/Brian_Josephson

I would say these people generally like to follow wherever curiosity leads them, without giving much thought about peer opinion, which is why they are the ones winning prizes for revolutionizing discoveries. They are freer to do so once the price is in and this may lead them any direction.

[eesmith]

A milligram dose is not usually considered homeopathic. A 6C homeopathic dilution, which is on the less potent end of homeopathic medicines, is 1:10^12.

Now, a gram vs. milligram would be between 2C and 3C (or 3X on the decimal scale) so it can be described on a homeopathic scale, but then again, full-strength of 0X or 0C can also be on that scale so I don't think this is the interpretation you mean.

FWIW, "Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial" at https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.... uses 1g and 3g doses and refers to the 30mg dose as "placebo". It's apparently hard to get the taste right with truly homeopathic doses.

> many studies not seeing effects are not actually giving people gram-megadoses

Pauling is seen as a quack when it comes to vitamin C because he claimed it could help treat all sort of things; for colds, for cancer, for AIDS treatment, for asthma, for mononucleosis, and for far, far more, as he uncritically lists every single positive connection to vitamin C in his 1987 book "How to live longer and feel better". https://archive.org/search?query=%22How+to+Live+Longer+and+F...

That makes it hard to know what studies you refer to, and certainly there are studies which did use gram-megadoses and failed to replicate or find support Pauling's findings, like:

Anderson TW et al, in "Vitamin C and the common cold: a double-blind trial", Canadian Medical Association Journal (1972) used 1-gram megadoses, with 4-gram megadoses at the onset of colds. "It was found that in terms of the average number of colds and days of sickness per subject the vitamin group experienced less illness than the placebo group, but the differences were smaller than have been claimed and were statistically not significant". https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940935/pdf/can...

Pauling's original study, with a smaller population and shorter time frame, suggested the benefits were far more significant, so should have been visible in that Canadian study, and that's only one of several >= 1 gram studies.

> Maybe it’s not double nobel laureate Pauling who was so wrong that he has pretty much become a quack in popular knowledge, but the fields of nutrition and perhaps medical science that are shoddy.

Do you think double-Nobel-Prize-winner Pauling was right that megadoses (10g) of vitamin C could treat cancer?

Because that was tested. "Failure of High-Dose Vitamin C (Ascorbic Acid) Therapy to Benefit Patients with Advanced Cancer — A Controlled Trial", https://www.nejm.org/doi/full/10.1056/nejm197909273011303 with 10 g per day.

Oh, but wait - Pauling then said vitamin C only worked on cancer patients who had not received already had chemotherapy.

Nope, still not the case: "High-Dose Vitamin C versus Placebo in the Treatment of Patients with Advanced Cancer Who Have Had No Prior Chemotherapy — A Randomized Double-Blind Comparison", https://www.nejm.org/doi/full/10.1056/nejm198501173120301 with 10 g daily.

Oh, but the problem is the Mayo Clinic doesn't follow Pauling's protocol, and didn't continue treatment beyond 75 days. https://www.science.org/doi/10.1126/science.1925592 .

When should other people stop listening to Pauling's claims?

So Pauling and Cameron did their own study to support the claim ... which was criticized for the lack of blinding and poor selection of controls. (ibid).

> it’s quite well known that marketing departments of the pharmaceutical industry have a lot of time on their hands to write those articles that benefit them

It's quite well known that people in the pharmaceutical industry, and their friends and family, also get colds, cancer, and more. Do you really think they are hiding a cure from their co-workers, friends, and family?

It's also well-known that the supplement industry makes billions of dollars, among other things, from actual homeopathy, and this money gives them lots of time to write those articles that benefit them.

Agreed about Josephson!

[armchairdweller]

Thanks for the writeup.

> Pauling is seen as a quack when it comes to vitamin C

Pauling has been portrayed as a nobel-laureate-gone-quack / example of "Nobel disease" in pop science media many times. Often by gullible people who are not actually scientists but more science(tm) promoters like podcasters. They don't usually limit it to the Vitamin C advocacy, but seem to like telling a story of a highly intelligent person "gone quack".

> "Mega-dose vitamin C in treatment of the common cold: a randomised controlled trial"

I don't have access to this but will check later.

> Anderson TW et al, in "Vitamin C and the common cold: a double-blind trial",

I've seen this before and quickly checked again (don't remember everything). They describe and show in Tables II and III a 30% marked-as-significant reduction in confinement to house, so apparently the severity of relevant cold symptoms is indeed strongly decreased. They say themselves that Pauling based his claims on studies showing 45% and 60% respectively (which you have not linked to for some reason). Even 30% is still well over the significance-and-usefulness threshold in my eyes at least, particularly if it comes from a study quite open about intending to "debunk" the perceived quackery. I would figure that the real number is somewhere in-between the advocates and these "debunkers". (Btw, in the discussion they made a weird 70s-boomer claim that consuming four ounces of vegetable and fruit juice per day is sufficient to prevent Vitamin C deficiency, and that 30mg Vitamin C per day is the basic requirement. Also, that they could not (or did not try to) really eradicate the confound of other health measures like other supplements taken is one of the typical problems with nutritional studies.)

About the cancer claims (which I agree should be treated with utmost suspicion, just like any cancer treatment): While I don't have strong stakes in the game to either support or "debunk" it, less than 75 days does seem to be on the short side for a serious disease for me. I wonder how this compares to other cancer medication studies with more profit in the game.

> It's also well-known that the supplement industry makes billions of dollars, among other things, from actual homeopathy, and this money gives them lots of time to write those articles that benefit them.

The supplements industry spends much more of that time and money on fake reviews on Amazon and other social media marketing. Seems to be much more effective for their consumer base than a long-form wikipedia article. Since the profits of the pharmaceutical industry for newly developed patented products are much higher, I guess they have some more money on their hands to hire a few "scientists" to write convincing-sounding long-form articles for pay.

> It's quite well known that people in the pharmaceutical industry, and their friends and family, also get colds, cancer, and more. Do you really think they are hiding a cure from their co-workers, friends, and family?

People in the pharmaceutical industry's marketing departments are hired and paid for writing supportive articles. I bet they are also made believe that they are doing the right thing(tm).

I first noticed suspiciously professionally written "debunk" Wikipedia articles during the Séralini affair - whatever you want to think about it; the time frame in which highly polished professional articles popped up was remarkable. Even otherwise pro-industry centrist-conservative media here got suspicious and wrote about potentially industry-written wikipedia articles. If you need any further convincing who writes WP when money is in the game, check out the article about the "well-recognized musician" Justin Bieber.

I'm not sure why this overall topic triggers so much. A bit more on topic again: Science had very obvious issues with information overload for long time and unfortunately this allows bad players and COIs to exploit the system (recommended reading, also for OPs link: "Science Fictions" by Stuart Ritchie). These developments are out in the open for everyone who is willing to see them. Particularly in recent years. This needs fixing, seriously; and I hope you see it and agree with this, and think along for solutions (as the solution will most likely be technological).

(The "homeopathic dosage" wasn't meant literally.)

[eesmith]

> Pauling has been portrayed as a nobel-laureate-gone-quack

Oh, certainly. I wanted to emphasize that the quackery was only in regards to his views on vitamin C.

> in pop science media many times

To be clear, it's also told in the scientific literature by people with chemistry and medical training.

> so apparently the severity of relevant cold symptoms is indeed strongly decreased

My previous comment wasn't meant to be conclusive about the experiments that have been carried out, but to point out how experiments using >= 1 gram doses have been done.

I did this because you criticized studies which used sub-gram doses. I have no problems with that viewpoint, but since >= 1 gram studies exist, you surely need to address their conclusions.

I pointed to the Canadian paper because it was the earliest one I could find to investigate Pauling's claim.

> so I would figure that the real number is somewhere in-between the advocates and these "debunkers".

That's not how statistics works!

Yes, that paper shows that a couple of the findings were statistically significant ... but also remember the XKCD 882 on "green jelly beans linked to acne" https://www.explainxkcd.com/wiki/index.php/882:_Significant - if you test enough random data, you'll find statistical correlations due to random happenstance.

You need to run the experiment again and see if the signal is still present, otherwise you're chasing statistical noise.

Which the Canadians did the next year. See "Vitamin C and the common cold: a double-blind trial" at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1947567/pdf/can... where figure 1 shows no statistical difference in "days indoors" for 0.25, 1.0, and 2.0 grams taken prophylactically (or 4g and 8g taken therapeutically), contra Pauling's suggestion "on theoretical grounds that the beneficial effects of regular vitamin C supplementation should be proportional to the size of the daily dose."

So that's another >= 1 gram study, from the same people. From what I can tell from other summaries on the topic, there were dozens of these >= 1 gram studies by the 1990s or so.

Surely these are more relevant to your rabbit-hole exploration than the sub-milligram studies you complained about, yes?

> They say themselves that Pauling based his claims on studies showing 45% and 60% respectively (which you have not linked to for some reason).

I did not link to them because I wanted to understand your objections to the attempts at replication using >=1 gram of vitamin C/day, given that I know they exist, as I showed by demonstration. Both you and I know those publications exist.

Here's what I think is a copy of the original 1961 publication by Ritzel, https://www.mv.helsinki.fi/home/hemila/CC/Ritzel_1961_ch.pdf , "Kritische Beurteilung des Vitamins C als Prophylacticum und Therapeuticum der Erkältungskrankheiten". I lack the German to read it, but Tabelle 1 doesn't seem to match Tabelle 2? That is, Tabelle 1 says the number of krankheitstage ("sick days") is 31 for the vitamin C group and 80 for the placebo group, but Tabelle 2, with the individual breakdown, says there were 42 krankheitstage and

Here's Pauling's description of Reitzel, from his 1970 book "Vitamin C, the common cold, & the flu" https://archive.org/details/vitaminccommonco00paul/page/44/m..." pp 43-44:

"He reported a reduction of 61 percent in the number of days of illness from upper respiratory infections and a reduction of 65 percent in the incidence of individual symptoms in the vitamin C group as compared with the placebo group."

That 61% is computed from Tabelle 1, "Anzahl Krankheitstage" at 31 days vs. 80 days for the placebo group. (80-31)/80 = 0.6125. But oddly, Tabelle 2's columns for "Anzahl Krankheitstage" add up to 42 and 119, respectively, so I think Tabelle 1 swapped the value for Krankheitstage and Einzelsymptome?!?! (Both are ~60% reduction, so this doesn't affect the conclusion.)

Also, note the short time - the vitamin C was only delivered for two 5-day ski camps, and those with cold symptoms on the first day were excluded from the study. If 60% were replicable, and not a statistical fluke or flaw in the methodology, it should be easy to see in other studies.

Note also that earlier on page 44 Pauling says that 200mg to students as a girls school in Ireland (it look like teenagers) reduced the severity and duration of colds ("Duration of the symptoms in catarrhal colds was reduced from 14 days to 8 days in the children receiving ascorbic acid."), so at this point he believes there is supporting evidence that 200mg (or perhaps 500mg for adult body weight?) is enough to show a noticeable effect.

Though Pauling is sloppy, saying "Wilson and Low in 1970" when it's "Wilson and Loh". Plus, here's Wilson criticizing Pauling's interpretation at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1795409/pdf/brm... shortly after the book came out:

"Nothing can therefore be concluded about the relationship of ascorbic acid metabolism and the appearance of cold symptoms in the different experimental groups from the results of this trial. ... by modern standards of clinical trial methodology [Tyrrell's trials] could not be classified as a well conducted clinical trial on the relationship between development of the clinical features of the common cold and the administration of supplementary vitamin C ... Dr. Pauling did not provide this critical evidence necessary for support of his hypothesis about the relationship between the administration of supplementary vitamin C and reduction of the symptoms of the common cold" - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1795409/pdf/brm...

> About the cancer claims (which I agree should be treated with utmost suspicion, as for any medicine):

Does his "double nobel laureate" affect your interpretation of his views on vitamin C and colds more than your interpretation of his views on vitamin C and cancer?

Anyway, if Pauling has stopped with Vitamin C and the common cold, I don't think he would have been seen a quack. Eccentric, sure, but was his doubling down to say it also treats cancer, and his tripling down to promotes how it may treat a host of other diseases, which made him a nobel-laureate-gone-quack.

> People in the pharmaceutical industry's marketing departments

Okay, think back to the 1970s when Pauling promoted vitamin C for the treatment of the common cold.

What treatments did people use for the treatment of the common cold? Aspirin was generic. acetaminophen (Tylenol) was generic. Ibuprofen was under patent, but competed against the first two. I think pseudoephedrine was generic? ("first characterized in 1889" says Wikipedia).

I don't see much in the way of patent profits there .. and I still don't know.

Who produced and sold vitamin C? (Hint: a paper I mentioned earlier end "We are grateful to Dr. J. Y. Gareau of Hoffmann-La Roche Ltd. for supplying the vitamins and placebo tablets.").

So, what did the pharma industry have to lose by promoting 1g consumption of vitamin C every day, for prophylactic use against the common cold?

Why would pharma profits prevent the military from using an effective cold treatment?

Why would pharma profits prevent the Soviets from using an effective cold treatment?

Why would pharma profits prevent the national school systems in Europe from providing vitamin C megadoses to their students?

> I first noticed suspiciously professionally written "debunk" Wikipedia articles during the Séralini affair

I have no idea what that means. My initial understanding of Pauling's megadose idea predates the existence of Wikipedia. Séralini seems to be a post-2010 thing? How does that affect any of the earlier published experimental results showing that megadoses don't have the clear effect that Pauling claimed, and that megadoses come with some side-effects.

> I'm not sure why this overall topic triggers so much.

Because there's oodles of published research over the last 50 years showing Pauling's ideas don't work like Pauling saying it would? Do you really want to say "pharam conspiracy" for something so easily tested that groups around the world evaluated the possibility? And that people like you can conduct yourself?

Who stands to profit from promoting Pauling's megadose hypothesis if it is actually false? And who promotes that idea the most?