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This is the talk page for discussing improvements to the Orthomolecular medicine article. This is not a forum for general discussion of the article's subject.

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sources

• Paul M. Insel, R. Elaine Turner, Don Ross Nutrition, Volume 1
• W. Edward Craighead, Charles B. Nemeroff The Corsini Encyclopedia of Psychology and Behavioral Science, Volume 3
• John W. Jacobson, Richard M. Foxx, James Anton Mulick Controversial therapies for developmental disabilities: fad, fashion, and science in professional practice
• Dónal O'Mathúna Alternative Medicine
• Ventegodt S, Andersen NJ, Merrick J (2003). "Holistic Medicine: Scientific Challenges". The Scientific World (3): 1108–16. doi:10.1100/tsw.2003.96.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)

proposed revision

I would like to replace the use in AIDS section in accordance with the criticisms noted here: http://en.wikipedia.org/Talk:Orthomolecular_medicine#POV

particularly what was noted in the first two sections:

Rath bakin' and egged on

This Rath section is a long standing eyesore that violates NPOV, and UNDUE, looks like a diatribe that is also simply redundant or misplaced. Although Rath might now be better classified as a fellow traveler among many flavors of nutritionists, his presence in orthomolecular medicine per se was roughly that of a sky rocket - Pffssst, Bang. Where many doctors and scientists have been larger and longer contributors. Rath was in and out within several years, 20 years ago. His "cellular medicine" dosages typically are a very small fraction of "fullbore orthomolecular" with his own patented additions. Also Rath has an emphatic anti-pharmaceutical position that is different than the "blended medicine" approach often recommended by founders like Pauling and Hoffer. I have not noticed that Rath has a current WP:RS that says he is still orthomolecular. If there is, I would worry that this article has begun a circular feed of opinion into the mainstream articles.--TheNautilus (talk) 10:23, 31 January 2012 (UTC)

Rath's later controversy as a POV vehicle of disparagement

As a matter of historical note I would think that the Orthomolecular Society would be an RS about who is notable, Matthias Rath is not even listed there, much less top 10-20 OMM figures. This article conflates Matthias Rath the young rising Pauling OMM acolyte in 1990-1992 researching a heart risk factor, with Matthias Rath a decade later, long defrocked from the Orthomolecular organization, practicing his version of nutrition under "cellular medicine" for AIDS. It thus gives a minor transient figure UNDUE attention, even more than Pauling and Hoffer in this article, for later methods/quantities not stated as orthomolecular. Sounds like a COATRACK to me. I thought my edit was still overgenerous.--TheNautilus (talk) 20:00, 31 January 2012 (UTC)

I would instead like to put the following after "Alleged Institutional Bias" - as was done in this article a long time ago:

Orthomolecular doctors

• Glen Dettman
• Abram Hoffer
• David Horrobin
• Archie Kalokerinos
• Carl Pfeiffer
• Matthias Rath
• Julian Whitaker

Orthomolecular scientists

• Abram Hoffer
• Linus Pauling
• Irwin Stone
• Albert Szent-Györgyi

I am looking for approval before making this change.Pottinger's cats (talk) 03:17, 24 January 2013 (UTC)

Multivitamin studies need improving

This section needs to be updated to include the latest study, which showed significant (~8%) decreases in cancer/mortality risk from long-term use of daily multivitamins. "A large-scale, randomized, double-blind, placebo-controlled trial (Physicians' Health Study II) of 14,641 male US physicians initially aged 50 years or older (mean age, 64.3 years), including 1312 men with a history of cancer at randomization, enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011."

The results are different from those of the smaller studies reported on Misplaced Pages.

http://jama.jamanetwork.com/article.aspx?articleid=1380451

173.73.121.64 (talk) 13:42, 21 June 2013 (UTC)SAH

No, it's a primary source and so fails WP:MEDRS (especially given it runs counter to the established consensus). Alexbrn 13:45, 21 June 2013 (UTC)

A simple Google reveals numerous secondary sources that cite this study.

As for "running counter to the established consensus"...it was a far more extensive study than those prior, so if anything its results are more valuable.

Furthermore, you are wrong that the two studies on the current page represent an "established consensus" in the medical community. They don't. The standard of care among primary care doctors is still to recommend a daily multivitamin for adults. Look it up if you're interested.

173.73.121.64 (talk) 13:54, 21 June 2013 (UTC)SAH

Correlation does not show causation. Even if it had in this case, we wouldn't know how. It could be, just to speculate wildly for a moment, that the effect is simply that reduced frequencies of micronutrient deficiencies leads to less craving and snacking... Anyhow, if there are good wp:MEDREV compliant sources, let's look at them and see which are the highest quality. LeadSongDog come howl! 15:57, 21 June 2013 (UTC)

I agree. Plus, a daily multivitamin is not the same thing as the megadose therapies that define "orthomolecular medicine". Keepcalmandcarryon (talk) 16:32, 21 June 2013 (UTC)

Hmm, just what "simple Google" query was it that generates "numerous secondary sources" citing this one? I'm not seeing anything obvious.LeadSongDog come howl! 16:53, 21 June 2013 (UTC)

The article drew a response here I can't access it - if somebody could it would be useful to know the thrust of it ... (Add: especially since the original article gets a lot of coverage in the Multivitamin article) ... Alexbrn 13:53, 22 June 2013 (UTC)

From the Commentary section of that article: "This study was well designed, well controlled and adher-ence to both interventions was good (>70% throughout most of the study period). Also, the interpretation of the results was measured, with the conclusions stating ‘a modest effect’. It is important to note however that this same trial showed no benefit for cardiovascular disease which tends to be an even more prevalent concern among middle-aged and older men (though it seems that within this sample the proportion of men with a cancer history was higher than that for cardiovascular disease, higher than that reported at baseline and higher than that of population norms).3 Thus, even though this was a very good study, these modest results and issues related to the representativeness of the study population and generalisability of findings call for caution. Moreover, it is questionable whether a difference of 1.3 events/1000 patient-years is clinically significant, espe-cially when supplementation would cost roughly $1800 over the balance of an average life, and the costs asso-ciated with additional visits to the chemist."

As an aside, I would like to see documentation that the "standard of care among primary care doctors is still to recommend a daily multivitamin for adults"; that would not jibe with authoritative sources such as this. Yobol (talk) 16:43, 22 June 2013 (UTC)

NIH Consensus document

The following quotes would appear to undermine the recent edits by Nitrobutane:

For the purpose of this statement, the term MVM refers to any supplement containing 3 or more vitamins and minerals but no herbs, hormones, or drugs, with each component at a dose less than the tolerable upper level determined by the Food and Nutrition Board—the maximum daily intake likely to pose no risk for adverse health effects.

This clearly limits the scope of their report. When they say that they do not find unequivocal evidence of harm from supplementation, they mean from these doses, which I take to be lower than those suggested by OM, by and large. Further, they go on to state:

There is potential for adverse effects in individuals consuming dietary supplements that are above the upper level.

So you see, they are not saying what you are suggesting they are saying. -- # ▄ 05:25, 18 August 2013 (UTC)

I agree; and would go a bit further. The doses recommended by orthomolecular medicine are clearly well outside those thought to be scientifically supported by the mainstream medical community. In that context, Nitrobutane's repeated reverts seem quite inappropriate. MastCell  06:03, 18 August 2013 (UTC)

These quotes 'undermine' nothing. The report does not show a majority consensus

either for or against the use of MVMs

Indeed they admit:

Within some studies or subgroups of the study populations, there is encouraging evidence of health benefits, such as increased bone mineral density and decreased fractures in postmenopausal women who use calcium and vitamin D supplements.

The recommendations in the OM field vary widely. It is misleading to state that OM 'by and large' recommends toxic doses of vitamins. Just because (you say) the report does not have the scope to find evidence of harm, does not mean that OM is by and large harmful. 'Potential' to misuse MVM, does not mean it happens 'by and large', or make the treatment invalid. Or that the majority of health professionals reject MVM. If the scope of the report really were too limited, then it would merely be an inadequate source - but it does manage to find benefits and adverse effects. Nitrobutane (talk) 17:09, 18 August 2013 (UTC)

The article doesn't, as far as I can tell, make a blanket statement that these practitioners recommend toxic doses of nutrients, and that doesn't really seem like what MastCell was saying either. The lead just says that the recommendations are not scientifically supported, and clearly there's the potential for hitting some upper limits which could have some negative health effects. A few benefits in subgroups doesn't really justify the broad recommendations and exaggerated benefits. The orthomolecular movement will also not really be able to take credit for future nutrigenomics advances. In any case, the orthomolecular group is hard to pin down exactly. There's the relatively respectable Linus Pauling Institute who are pretty cautious about their statements and use the word 'orthomolecular' sparingsly and then there's the more sketchy group associated with doctoryourself and the Journal of Orthomolecular Medicine, who are much more outspoken about the 'orthomolecular' concept. I would recommend that you really stop and re-evaluate your approach. This particular topic doesn't seem to be a good fit for you on Misplaced Pages right now, as you seem very emotionally invested. Incidentally, the article (and lead) is a bit lacking with regard to safety, but it's a complicated topic; last I I recall the vitamin E was profiled (and may have even showed a dose-response relationship) as the most harmful one with some bad recommendations and defensiveness (example) behind it. II | (t - c) 07:41, 19 August 2013 (UTC)

Please do not be missing the main point I am trying to make. The introduction to the article contains the phrase:

The majority of medical and scientific experts reject these claims

and adds a source to lend itself the air of credibility and solidity. That source, however (the NIH consensus document) admits that there are risks:

However, several other studies also provide disturbing evidence of risk, such as increased lung cancer risk with beta-carotene use among smokers.

as well as benefits:

Within some studies or subgroups of the study populations, there is encouraging evidence of health benefits, such as increased bone mineral density and decreased fractures in postmenopausal women who use calcium and vitamin D supplements.

concluding:

Finally, the present evidence is insufficient to recommend either for or against the use of MVMs by the American public to prevent chronic disease. The resolution of this important issue will require advances in research and improved communication and collaboration among scientists, health care providers, patients, the pharmaceutical and supplement industries, and the public.

The consensus document does not find against MVMs - it does not represent 'majority rejection', and is in fact a much more balanced and enlightened view than the phrase in the introduction is trying to imply. I find that whoever added that phrase to the Orthomolecular Medicine article acted in a fundamentally dishonest way. Nitrobutane (talk) 23:09, 21 August 2013 (UTC)

Ideally, the source would be more targeted towards orthomolecular medicine practice in general. However, it is a niche which doesn't attract much specific critical attention. The point that the NIH makes it that the evidence does not support broad claims of healing from nutritional supplementation. Are you saying that orthomolecular medicine does not make major claims, such as curing heart disease with vitamin E (absolutely zero scientific support but still a common claim), niacin for schizophrenia (ditto), vitamin C for cancer (ditto), and various other major claims? There are certainly intriguing nutritional interventions, but these are generally acknowledged by mainstream medicine (as the NIH document shows) and aren't what sets orthomolecular nutrition apart. II | (t - c) 03:48, 22 August 2013 (UTC)

Vitamin C huh? Just for the record: . You say 'the evidence does not support broad claims of healing from nutritional supplementation'. The wiki article says 'The majority of medical and scientific experts reject these claims'. Sounds similar, untill you realize the NIH document says 'the present evidence is insufficient to recommend either for or against the use of MVMs'. The NIH consensusn document provides a balanced view, but the language of the lead is trying to turn it into flat rejection. It is still misleading. Better if it is changed to:

Although the majority of medical and scientific experts do not support these claims, there is evidence that in middle age and later certain supplementation can provide substantial health benefits and reduce the incidence of cancer. The NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention concluded: ″the present evidence is insufficient to recommend either for or against the use of MVMs by the American public to prevent chronic disease.″

--Nitrobutane (talk) 03:50, 23 August 2013 (UTC)

Regarding vitamin C: 3 'cases', in a 2006 study. That's not much. If I recall correctly, there was a Phase I of intravenous in the past few years which found no effect, which you should perhaps dig up. Seems like a while for there to be no further breakthroughs, don't you think? As far as the NIH statement, the orthomolecular community makes specific claims. These are not proven, and in some cases they are specifically disproven, such as vitamin E and heart disease and niacin for schizophrenia. In fact these two claims form a major part of their history and philosophy. Therefore, it is fair to say that these claims (of benefit) are rejected. If the claim was simply 'maybe useful in a few situations', that probably wouldn't be rejected, but that's not what the proponents claim. Certainly if someone is deficient in vitamins, they will benefit from supplementation, and I personally think that time and additional research will show there to be a fair amount of benefit to be had there in various subpopulations who, while not obviously deficient, are on the low end of nourishment (e.g., iron for restless legs, selenium for cancer). But the community makes other claims. Go check out doctoryourself.com if you don't believe me. II | (t - c) 04:00, 23 August 2013 (UTC)

Nitrobutane, please see WP:REHASH. -- # ▄ 04:05, 23 August 2013 (UTC)

'If I recall correctly, there was a Phase I of intravenous in the past few years which found no effect, which you should perhaps dig up.' Yeah. 'If I recall correctly, there was a study which contradicts your study, perhaps go dig it up'. Very helpful. I don't care really. To me this seems to sidetrack the whole discussion. Somehow degenerated into a debate on orthomolecular medicine in general. What I am saying is the NIH document does not provide evidence of rejection, and the original writer is pretending it does. The truth lies somewhere in between, but the writer is pretending otherwise. Trying to make the whole article look bogus, using a source which does not actually support that view. --Nitrobutane (talk) 04:42, 23 August 2013 (UTC)

in other words, the source is irrelevant, and it is being misrepresented as saying something it is not saying. then I will change the text to this, as I have indicated before:

Although the majority of medical and scientific experts do not support these claims, there is evidence that in middle age and later certain supplementation can provide substantial health benefits and reduce the incidence of cancer. The NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention concluded: ″the present evidence is insufficient to recommend either for or against the use of MVMs by the American public to prevent chronic disease.″

to better represent the situation and the NIH Consensus document. — Preceding unsigned comment added by Nitrobutane (talk • contribs) 02:12, 24 August 2013 (UTC)

If it's not relevant, why would a more extensive quoting, out-of-context, be better than simply leaving the reference or claims out entirely? -- # ▄ 02:56, 24 August 2013 (UTC)

I added an additional cite to Aaronson 2003 for the claim. The wording could perhaps be improved a little, as the way it is worded suggests that correcting nutritional deficiencies isn't medically necessary. Clearly, correcting deficiencies improves health enormously; the question is whether these particular purported deficiencies exist. II | (t - c) 02:45, 26 August 2013 (UTC)

Vit C

Please see User_talk:Jamesx12345#orthomolecular_medicine and User_talk:198.189.184.243 for a debate regarding the efficacy of Vit C in treating cancer. The other user is currently blocked, but will likely have something to say when it expires. As a student of Ben Goldacre, I am skeptical, but whether there is a point to be made here, I don't know. James12345 18:54, 22 August 2013 (UTC)

I think there are a number of issues in these edits:

• the claim about "a key othomolecular modality" in the IP's edit seems to be pure OR, as this is not something the sources say
• any claim or implication about human health needs to be sourced to a WP:MEDRS-compliant source, which these aren't, so their use for suggesting there is worthwhile research acitivity here - against the grain of the medical/scientific consensus - is quite bordlerline ...
• ... nevertheless, the point made in the first source (Ohno et al), that "... two randomized clinical trials with oral ascorbate conducted by the Mayo Clinic showed no benefit (6, 7). These negative results dampened, but did not permanently extinguish, interest in ascorbate therapy or research. Some research groups conducted rigorous research, particularly in the area of administering mega-doses of ascorbate intravenously" seemed fair enough, and this is reflected in the version of the text which currently stands. Alexbrn 20:07, 22 August 2013 (UTC)

Thanks for that. I've requested protection on the grounds that it is easier to block a disruptive account than an IP, but this is always going to be harder to police than say, homeopathy or astrology. James12345 21:12, 22 August 2013 (UTC)

• Agree with Alexbrn. The article should not overstate the case for the continued interest in vitamin C even if there's a medical review out there which promotes it. Vitamin_C_megadosage#Cancer is fair. II | (t - c) 01:34, 23 August 2013 (UTC)

Per the WP:NOTAFORUM specification, I will not be posting the commentary where I attempt to make a lengthy case for orthomolecular medicine that I did here: . Instead, I will just make commentary about the subject of this - Vitamin C and cancer. With that said, Ben Goldacre has been mentioned, a source that counters his views on this is: http://www.lef.org/abstracts/index.htm

Now, on to the crux of this issue. The point of the reviews is that intravenous administration gives a much higher plasma saturation than oral, a level of saturation necessary to achieve an antitumor effect, and thus the Mayo Clinic studies are a pseudo-test. This was verified by a 2004 NIH pharmacokinetic study that concluded: "Oral vitamin C produces plasma concentrations that are tightly controlled. Only intravenous administration of vitamin C produces high plasma and urine concentrations that might have antitumor activity. Because efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated.": http://www.ncbi.nlm.nih.gov/pubmed/15068981

I would also like to provide an anecdote. I can understand the objection to anecdotes, and I acknowledge that promoters of quack cures are apt to provide anecdotes instead of studies, and this is problematic because it is difficult to isolate one factor from a multitude of factors that may have been responsible for recovery. Still, there are some cases from which we can clearly isolate the therapeutic effect of one agent. The following is an example, it concerns a man from New Zealand who was at death's door from swine flu and leukemia, but his family had the doctors intervene with iv vitamin c administration. He recovered completely. This was the isolated causative factor that did it, you can see the following news story on this: http://vimeo.com/23598532

I agree that the article should not overstate the case for continued interest in vitamin c, but the research groups, including the authors of the 2004 NIH pharmacokinetic study, suggest that the role for vitamin c in cancer treatment be reevaluated. Therefore, the revision of the commentary that I suggest is as follows. I think it is perfectly reasonable as it does not overstate the case, but merely notes the results of current research from notable sources. It also accurately reflects the content of the reviews. I also think that adding in the pharmacokinetic study as a third reference would be a good idea:

Some research groups have recently suggested that the use of vitamin C in cancer treatment should be reevaluated, as evidence has emerged that intravenous administration might produce the pharmacological concentrations necessary for an anti-tumor effect that oral administration does not.198.189.184.243 (talk) 18:13, 16 September 2013 (UTC)

First of all, 2004 is not "recent". It's nearly 10 years ago. Has anyone actually followed up on their observation in the intervening 10 years? If not, then presumably we'd be wrong to assign their paper undue weight. MastCell  18:28, 16 September 2013 (UTC)

There is some marginal interest in intravenous vitamin use (which is not, N.B., "orthomolecular medicine" as we define it) - and the article mentions this as an aside, without giving undue weight. The balance is right as it stands; but your edit overcooks it while blurring the distinction between intravenous investigations and the discredited oral therapy (which is not being "reevaluated"). Alexbrn 18:29, 16 September 2013 (UTC)

Never mind, I've answered my own question. A more "recent" 2008 clinical trial actually followed up the 2004 study (PMID 18544557). Were you (the IP) aware of this study, and does it appear in your LEF-approved list of papers? I ask because this study failed to find any anti-cancer effect of high-dose IV vitamin C.

So perhaps the text should read: "A 2004 manuscript suggested that intravenous vitamin C should be re-evaluated as an anti-cancer treatment, since IV administration results in significantly higher serum concentrations than oral administration. However, a subsequent trial using high-dose intravenous vitamin C found no evidence of any anti-cancer effect." MastCell  18:56, 16 September 2013 (UTC)

I suggested above that someone look into the follow-up. It's a bit complicated: there's been at least 3 Phase I studies apparently, and while it does not look very promising, there's still hope that in combination it is synergistic (according to Monti et al 2012 while Stevenson et al 2013 again found no objective response). There might be a review out there which puts it into decent context but I doubt I'd have access to it. II | (t - c) 20:16, 16 September 2013 (UTC)

Thanks for supplying those additional references. I hadn't seen the Monti paper. I'm familiar with the Stephenson paper, but have been conditioned by personal experience and reports like this to view anything coming out of Cancer Treatment Centers of America with extreme skepticism. I suppose that's neither here nor there; the bottom line is that, as you note, neither trial found any evidence of objective anti-tumor responses, so I'm not sure why the authors continue to believe that there's synergy. I'm also unconvinced of the wisdom of proceeding to a Phase II trial in the absence of any documented tumor responses in Phase I, but such is life. MastCell  20:25, 16 September 2013 (UTC)

Just piggybacked on the paper you found so thanks! I seem to distantly recall another negative trial out of Puerto Rico. I can think of areas where I'd rather put the money. On the other hand, this has gone on so long with such hype that it would be nice to conclusively shut the book, if possible. II | (t - c) 20:55, 16 September 2013 (UTC)

Thank you - your dismissals are not as strong as you think, and I can still think of a way the article can be improved. Before I get into that, I would like to note that none of the information, pro and con, that I obtained for this particular database, was garnered from the LEF database, so it still remains a viable database for nearly every substance an orthomolecularist would use.

For the Monti paper, in response to Mastcell's comment, "neither trial found any evidence of objective anti-tumor responses, so I'm not sure why the authors continue to believe that there's synergy", I'd like to provide an actual exerpt from the text of the writeup on the trial: "CT images at the beginning and end of 8 weeks of treatment revealed that primary tumor size (target lesion) decreased in 8 of 9 subjects; was stable in the one subject who did not have a decrease; and specifically decreased in the three subjects who received the highest ascorbic acid dose (see Table 3 and Figure 3). Clinically, these findings are not typical with treatment using gemcitabine alone or with gemcitabine plus erlotinib , , , , , .

The behavior of non-target lesions also was concordant. In the highest ascorbate dose group, non-target lesions were either improved or stable, and 7 of 9 patients who had pre and post treatment CT scan evaluations had stable or improved non target lesions. However, since 3 additional patients died from rapid progression of the disease the overall result would suggest that 7 of 12 patients had stable disease. The data are consistent with observed synergy between gemcitabine and pharmacologic ascorbate in cell and animal experiments ."

The reviews currently cited note the following evidence suggesting a possible effect at least as an adjunct to traditional therapies. See, for instance, the study "Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues.": http://www.ncbi.nlm.nih.gov/pubmed/16157892?dopt=Abstract

One review also notes the fact that in animal studies, it has been shown to have a significant effect, as in this study on mice: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516281/

Well documented case series have shown significant effect - as in this one: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1405876/, which corroborates items like this article, which states that "In addition to the increase in survival times, the administration of large doses of ascorbate seemed to improve the quality of life.": http://www.ncbi.nlm.nih.gov/pubmed/6811475 Both of these items are profiled in one of the reviews.

These have all been noted in the article. The edit I propose, to accurately reflect the content of the reviews is - "In the early 2000s, some research groups argued that case series and pharmacokinetic and animal studies suggested that intravenous administration of vitamin C might have an anti-cancer effect that oral administration did not. As of September 2013, 5 Phase I trials have been carried out. Two of these Phase I trials showed a synergistic effect with traditional chemotherapeutic treatment, two demonstrated no objective anti-tumor response, and one only demonstrated response in 1 out of 24 patients."

If this edit is reverted, I hope wikipedia editors take note of the WP:BRD policy, and make meaningful modifications on this talk page.198.189.184.243 (talk) 00:26, 24 September 2013 (UTC)

I think you're interpreting the Monti study incorrectly, or at least very selectively. First of all, nearly half of the enrolled patients dropped out of the study or otherwise failed to complete it - a major red flag. Secondly, none of the patients had a response by RECIST criteria. None. Zero. Stable disease is not a response, and I'm not sure why the reviewers let the authors get away with moving the goalposts and implying that it is.

It's also really silly to claim that these results are "not typical" of those seen with gemcitabine +/- erlotinib. In fact, gemcitabine/erlotinib has a reported response rate of ~25% (vs. 0% for the Monti study), and a stable-disease rate of ~60%—statistically equivalent to the stable-disease rate of 50% in the Monti study (e.g. PMID 20044638). So Monti et al. are right that their results aren't "typical" - they're actually worse than what one might expect with gemcitabine/erlotinib alone. One could reasonably conclude from their findings that ascorbate actually impairs the effectiveness of gemcitabine/erlotinib—which is biologically plausible, given ascorbate's role as an antioxidant.

So no, I don't agree with your proposed revision to the article. MastCell  03:27, 24 September 2013 (UTC)

Regarding the statement "I think you're interpreting the Monti study incorrectly, or at least very selectively", I think the same applies to you. The fact that some people dropped out of the study means that it is not very helpful to make conclusions about them in the study (e.g. - you state that the stabilization rate in the Monti study was 50% - this includes the people who dropped out. However, if we include the people who actually completed the study, 7/9, or 77% had stabilization - higher than the 60% average of treatment with the traditional drug alone). Also, your statement about the nature of the stabilization (purporting 0% regression) can be challenged by figure 3 of the trial: http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029794.g003/originalimage, showing that there was regression, but regression lower than the required standards of RECIST criteria for it to be reported as such. Partial response criteria is at least 30%: http://en.wikipedia.org/Response_Evaluation_Criteria_in_Solid_Tumors#Response_Criteria, so your statement about ascorbate lowering efficacy seems unwarranted, as gemcitabine/erlotinib do not qualify as drugs evoking partial response, according to the study you gave.

There are some other interesting observations from the study that are noteworthy: "Overall, the safety data do not reveal adverse events other than what might be expected for progression of pancreatic cancer and/or treatment with gemcitabine and erlotinib. Deaths of three patients who died before completing the study were attributable to underlying and rapidly advancing disease, as affirmed by the Data Safety and Monitoring Board. primary tumor size ... specifically decreased in the three subjects who received the highest ascorbic acid dose. It is noted that RECIST 1.0 criteria for stable disease are inclusive of a 19% increase in target lesions . Other studies of gemcitabine efficacy in pancreatic cancer that categorize disease as stable do not provide details concerning target lesion increases under 20%, meaning that subjects with target lesion size increases up to 19% are still considered stable disease. Therefore, the importance of our finding of target size decrease in 8 of 9 subjects may be underestimated. In particular, unlike many cancer therapies, ascorbate does not appear to have toxicity on rapidly dividing normal cells such as those in intestine cells, hair follicle cells, and bone marrow. Because of the absence of apparent tissue toxicity, effects of ascorbic acid treatment on human tumors might be expected to be more gradual, and as a corollary to require longer treatment. This possibility is consistent with observations from case reports of patients who received intravenous ascorbic acid as treatment for several types of cancers. Given the possibility that longer ascorbic acid treatment is necessary to see disease improvement by RECIST 1.0 criteria, and the somewhat encouraging findings in the nine subjects in this trial, studying a longer treatment period at the 100 gram dosage seems warranted."

Animal studies also support synergy, like this one, which concludes that "Gemcitabine-ascorbate combinations administered to mice bearing pancreatic tumor xenografts consistently enhanced inhibition of growth compared to gemcitabine alone, produced 50% growth inhibition in a tumor type not responsive to gemcitabine, and demonstrated a gemcitabine dose-sparing effect. These data support the testing of pharmacologic ascorbate in adjunctive treatments for cancers prone to high failure rates with conventional therapeutic regimens, such as pancreatic cancer." (emphasis added): http://www.ncbi.nlm.nih.gov/pubmed/21402145

There is a view that ascorbate interferes with chemotherapy - a view refuted with this systematic review: http://www.ncbi.nlm.nih.gov/pubmed/17367938

And particularly with ascorbate administered at high doses intravenously to subjects with cancer, there are differences in pharmacology. See the study "Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice": http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2516281/ - the pharmacology of this discrepancy (given the different physiological environment) is explored here: http://www.sciencedirect.com/science/article/pii/S0304419X12000509

Recall again an article given above showing how ascorbate at very high levels can act as prodrug to deliver a significant flux of H2O2 to tumors, and also the fact that "ascorbate does not appear to have toxicity on rapidly dividing normal cells", quoted in the above trial. Ascorbate has different action in different environments.

As far as synergy is concerned, another trial also shows some efficacy for ascorbate treatment, as admitted in the conclusion: http://link.springer.com/article/10.1007/s00280-013-2070-8

I will admit bias, as I was witness to my mother's suffering with chemotherapy, but at the same time acknowledge that there is a dearth of data on viable alternatives to standard treatments. Because of this, I gained some interest in complementary (and, as we now know, in some cases, synergistic) treatments like ascorbate, after the period of her treatment, so that others would not suffer as much. It is thus important to note that there are 2 studies showing improved quality of life, that show that while it does not have value as an alternative treatment, it does have value as a complementary treatment. One of these is this: http://www.ncbi.nlm.nih.gov/pubmed/6811475, and also there is this: http://www.ncbi.nlm.nih.gov/pubmed/22021693, which concludes, "Complementary treatment of breast cancer patients with i.v. vitamin C was shown to be a well tolerated optimization of standard tumour-destructive therapies, reducing quality of life-related side-effects."

I was banned from editing the article under per WP:ARBPS, under the pretext that I was "pushing pseudoscience" (there was a premise that I was "edit warring", the data does not support that - see especially the bottom): http://en.wikipedia.org/Wikipedia:Administrators%27_noticeboard/Edit_warring#User:198.189.184.243_reported_by_User:UseTheCommandLine_.28Result:_Topic_ban_under_WP:ARBPS.29

I still think I have the right to make this point on the talk page. I do not see how that is forbidden, from what I see, only edits to the article are forbidden - though, I feel, under illegitimate pretexts, since the fact of reconsideration being pushed in mainstream journals: http://advances.nutrition.org/content/2/2/78, http://ar.iiarjournals.org/content/29/3/809.long - means that the WP:ARBPS policies do not apply in this case. My initial concern was to accurately reflect the reviews (which are not accurately reflected in the article at this time, and as such, diminish wikipedia's credibility as an encyclopedia).

Phase I trials are discouraged under WP:MEDRS, so I don't think we need to put them in. I think a better edit (and another user would have to put it in), in light of the discussion above, keeping everything simple, would be (I am using pseudo-wikipedia code here - the reasons the reviews suggest reevaluation are pharmacokinetics, case series, animal studies, and other pharmacological observations):

"Some research groups have recently suggested that the use of ascorbate in cancer treatment be reevaluated.( http://advances.nutrition.org/content/2/2/78 )( http://ar.iiarjournals.org/content/29/3/809.long ). A prospective cohort study showed that complementary treatment of cancer patients receiving traditional chemotherapy and radiotherapy with intravenous vitamin c improved quality of life.( http://www.ncbi.nlm.nih.gov/pubmed/22021693 )"198.189.184.243 (talk) 22:01, 24 September 2013 (UTC)

1. http://www.ncbi.nlm.nih.gov/pubmed/12540414
2. http://www.ncbi.nlm.nih.gov/pubmed/23162860
3. http://www.ncbi.nlm.nih.gov/pubmed/17332802
4. http://www.ncbi.nlm.nih.gov/pubmed/12540414
5. http://www.ncbi.nlm.nih.gov/pubmed/23162860
6. http://www.ncbi.nlm.nih.gov/pubmed/17332802

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