Talk:Orthomolecular medicine/Archive 10

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Which RSMED "reliable source" to believe? Hmmm?

For all my medical career it's a well-known fact that it's a well-know fact that saturated fat intake contributes to atheromatous cardiovascular disease. Every major medical body has said this for 30 years and more. Of course, 30 years before that (taking us back to 1950) there was no official position on diet and coronary disease, until 1953 when Ancel Keys published his 6 country study. A timeline is here, for those of you who didn't live through a lot of this: [1] from 1956 until the official US government guidlines on fat intake were codified, saturated fat was the badguy. McGovern's Senate Select Committee issues the final version of the Dietary Guidelines for Americans in 1977, in which animal fat is the primary Bad Thing. The evidence: a bunch of epidemiology in which a lot of societies that had the "wrong numbers" (Polynesians who live on coconut, and French who eat butter and fois gras) were selectively ignored. The animal studies were pitiful, and generally malnurished a bunch of animals with hydrogenated oils and no EFAs. Nobody cared. The reliable government sources considered this data reliable, due to their previous bias, due to Keys.

Okay, fast-forward to last year:

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Am J Clin Nutr. 2010 Mar;91(3):535-46. Epub 2010 Jan 13.

Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.

Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Children's Hospital, Oakland Research Institute Oakland, CA, USA.

Comment in:

   Am J Clin Nutr. 2010 Mar;91(3):497-9.
   Am J Clin Nutr. 2010 Aug;92(2):459-60; author reply 460-1.
   Am J Clin Nutr. 2010 Aug;92(2):458-9; author reply 459.

BACKGROUND: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. OBJECTIVE: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. DESIGN: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. RESULTS: During 5-23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. CONCLUSIONS: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat.

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That's a GIGANTIC meta analysis. Now, the "reliable sources" told us one thing in 1953, something else quite different in 1977, and now we're back again to 1953. How can that not make you cynical? The 4 food groups were killed by the low fat people. The 4 food groups had no backing anyway. But neither did the low fat food pyramid. This is fail after fail after fail.

And all this cynicism is not just that I'm a medically unsophisticated person following along in the newspapers. I've been deep in the medical journals following the mechanisms and formal recomendations for years. And recognizing their bias. But unable to do very much about it. Sometimes they even suceeded in fooling me: I can't know everything and my instincts are not always good. But I was ahead of a lot of THIS game.

So, watch that the same kind of thing doesn't happen to you, in any field in medicine where there are no randomized prospective controlled primary prevention studies. (Ornish isn't one). You can get major egg on your prefessional face this way. SBHarris 06:48, 15 April 2011 (UTC)

First thing, just something about which you should be aware, ==Heading== creates a break and heading. You're kind of creating arbitrary breaks, when I think you just wanted to draw a double line. Anyways, that's the thing about science...it changes with new data. I'm all right with it, because it doesn't cause me to be cynical, just openminded. Pseudoscience is never open to change, and cannot be falsified. I'm not sure what your point is, but just because no one has shown that massive doses of vitamins does anything but give us very vitamin rich urine, doesn't mean they will. Moreover, and the fallacy of any epidemiological study is that it identifies correlation, but it does not explain causation. There could have been some other co-determinant factor, mainly that a fatty diet usually leads to fat people who have a higher propensity to cardiovascular disease. Because it's not an epidemiological study that shows overweight leads to heart disease, we can show causality.

Anyways, you are absolutely right. No randomized clinical trials means it's next to impossible to make any type of statement. However, it would be a logical fallacy to say that "well, since there is no clinical trial, it doesn't mean that that megavitamins don't work." Well, that's the old "the absence of evidence doesn't mean evidence of absence." Well, in fact, the absence of evidence is evidence of absence, using evidence in the truest sense. OrangeMarlin ^{Talk• Contributions} 03:32, 16 April 2011 (UTC)

Sorry, I was trying to use a double line to set off text and should have used the single.

Yes, assuredly, if you have no GOOD evidence, then you have a problem-- but the question remains of what to DO, in that case. Some people, influenced by animal studies, epidemiology, or small prospective clinical trials, are "interventionists" (especially since vitamins and other nutritional treatments are cheap). Others, with other prior assumptions, choose to do nothing. It's not as though there NO evidence on prospective randomized vitamin/mineral supplementation and mortality: there is, and the news, as I read it, is either neutral or good, with the exception of beta-carotene. [2]. The famous meta analysis of vitamin E studies by Miller et al. in 2005 only found a significant increase in all cause mortality in the > 150 IU studies (which were almost all 400 IU studies) and if you go with the best evidence, that merely means everybody should not take 400 IU vitamin E. Fine. And you can note that Miller et al. did that high/low split post-hoc on this evidence (since the total vitamin E prospective study data showed no effect on mortality), which in statistics is a no-no. You can't do that kind of split, unless you intended to do it (and said you did) BEFORE you did the analysis. You can't just massage your data until you find a subgroup that has some P= 0.035 effect, because you generally can go until you find something. Miller et al., meet signor Carlo Bonferroni.

And why, I ask, is vitamin therapy required to have a better standard of evidence for treatment than many drugs? For example, the prospective randomized WHS trial of postmenopausal women on vitamin E [3] showed a 24% decrease in sudden cardiovascular death (not MI or stroke, however, so this was probably P.E.). Which makes sense as vitamin E is probably like a small dose of coumadin, with effects on vein clotting only. There was no difference in all-cause mortality, but the study wasn't powered for it. So why aren't doctors routinely giving all post-menopausal women vitamin E, to prevent embolism and sudden death? The evidence is better for this than prevention of sudden death (or any kind of death) in this group using (say) fibrates, and yet doctors who give out fibrates (which you can see advertised in TV, there's so much money in it) are considered "mainstream," whereas I have the feeling that doctors who "prescribe" vitamin E for any purpose, are considered by many to be orthomolecular or megavitamin or naturopathic quacks. I am arguing for use of the same QUALITY of evidence for any decision, and I smell double-standards. How many of our modern drugs have been shown to decrease total mortality, even for the subgroups of persons they are intended for, in randomized clinical trials? Not very darn many. And yet, they are used, and this is defended as "reasonable," never labeled as quackery. What was that you were saying about absense of evidence? It's a relative state, is it not?

To put it bluntly, why is it that making recommendations on the basis of not-very-good epidemiological evidence (as the mainstream has been doing for restricting satutated fat intake, for 30 years) is okay, but if you make recommendations for vitamin supplementation on the same quality evidence, you're an unscientific quack? What's the difference, philosophically? Example #2: do you know the history of hormone replacement therapy? Again, why no accusations of quackery on the basis of insufficient evidence, there, especially for progestins, which were used freely in HRT since 1973, and in combination with Premarin since 1998? SBHarris 21:22, 16 April 2011 (UTC)

I'm confused by your argument. Here's the conclusions of the study authors: "The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women." Where does it show a 24% DECREASE in cardiovascular death. I see a change from 2.4% to 2.6% between groups, a statistically insignificant difference. And I can tell you that the FDA would reject an NDA for any drug that showed no difference. I'm a little confused by your comments because I swear I could pick out statements that blast megavitamin/orthomolecular or you're supporting it. Maybe I need more coffee. OrangeMarlin ^{Talk• Contributions} 03:03, 17 April 2011 (UTC)

You're looking at figures for major cardiac events. Look at the endpoint table in the link I posted: [4] Do you see the figures for "cardiovascular mortality"? Now read the author-conclusion you just posted: "The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women." From this, the authors come to the conclusion that vitamin E has no place in prevention of cardiovascular disease or cancer. To which I say: Fine, but in medicine we'd like to prevent DEATH, not just diagnosed "disease." Most of the women in this study who died a cardiovascular death-- about 75-80% --did NOT die of a diagnosed fatal MI (identified disease before death-- this was RARE) or fatal stroke (also comparitively rare), but rather of sudden cardiovascular death too sudden for certain diagnosis of MI (ST-changes, etc) to be make, or else embolism. The kind of thing where the woman falls dead and can't be resuscitated, and although her doc is pretty sure the death is cardivascular, nobody can say just where. But the patient still ends up dead, which you would think is the important thing, no? Total deaths in this study were overwhelmed by cancer deaths (3 times as common as cardiovascular deaths), which vit E didn't affect. Vit E did have a significant effect on the rest of the deaths (RR 0.76 with confidence limits 0.59 - 0.97) but this failed to gain the authors' attention when it came to recommendations, which they summarize in terms of less interesting categories. They chose to focus on total deaths (no effect) and "cardiovascular EVENTS" (where again the non-fatal events were 4 or 5 times as common as the nonfatal ones) and thus again wash them out (so no effect). Vitamin E has little effect on non-fatal cardiovascular events but has a large impact on fatal ones. Nevertheless the study authors chose to look at the "big picture" each time, and fold in the part of cardiovascular disease which is non-fatal, with the cardiovascular disease that is. The study actually suggests that you should take vitamin E if you're postmenopausal woman and care about cardiovascular death, but perhaps not if your major care instead, is being diagnosed with a cardiovascular "event" or disease. I suppose it comes down to which thing concerns you more: getting a new CV disease diagnosis, or suddenly dying from one.

Contrast this with use of fibrates, where the situation is exactly flipped: fibrates prevent 10-13% of cardiovascular events in their targetted hypertriglyceridemic groups (depending on severity) but have not yet been found to prevent total cardiovascular deaths, even in meta-analysis. [5] It seems the less like the event is to kill you, the better fibrates work on it (in stark contrast to vitamin E). Yet billions of dollars are spent on fibrates, and they are widely recommended and prescribed. That's a double standard. This note is getting too long already, but that's enough data to illustrate my position, which neither for or against MVT, naturopathy, OM, or orthodox medicine in all things, per se. Rather, what I want (on WP and in the real world) is for the same standards to be applied to "orthodox medicine" as to "alternative medicine". And I want it acknowledged that that the pharmaceutical industry (and the money it supplies to fund studies, which is equal to the NIH funding) has a very unfair and biased impact on what we "know" (or think we know) in medicine, and what is recommended in journals. That needs to be acknowledged, but rarely is. SBHarris 19:58, 17 April 2011 (UTC)

Not to completely squash your hopes, but other large clinical trials have shown that Vitamin E actually increases the rate of cardiovascular mortality. The authors of the study state: "The WHS finding of a decreased cardiovascular death rate with vitamin E, as well as decreased major cardiovascular events among women aged at least 65 years, differs from the totality of evidence and should be explored further." They were concerned it was just a statistical anomaly. A recent trial, HOPE-TOO, has shown an INCREASED rate of cardiovascular events and death. That's why medicine never relies on one report and study to make a conclusion. Furthermore, we would logically expect a reduction in cardiovascular events which might lead to death. So, if I could make a strong recommendation. Don't use one study to make a conclusion. You've got to read all of the studies. Also, the raw data can't be equivocal, as it is here. OrangeMarlin ^{Talk• Contributions} 20:40, 17 April 2011 (UTC)

You see, this is why we're having problems, and is a great example of why WP also fails to evaluate sources well, despite RSMED. Evaluating studies is a tricky thing. For example, here you're giving me an incorrect result of a far smaller study in a completely different population, and suggesting it might "quash my hopes." No, it doesn't work that way. Here are the facts: The Ongoing Outcomes (TOO) part of the HOPE trial = "HOPE TOO" [6] did NOT find that vitamin E "increases the rate of cardiovascular mortality." I know of no single study that does, and the meta analysis finds a somewhat cherry-picked effect and is discussed above. What was found in HOPE-TOO (but no other single vitamin E study that I know of) was a increased incidence of congestive heart failure in the vitamin E group, but no statistical increase in any other endpoint. Okay, perhaps also a statistical anomaly-- we don't know. The p was .03 and .045 for hospitalization for this. It was "counted" as significant because the authors had previously decided it was an endpoint. The decreased incidence of lung cancer in the E group (p = .02) was larger, but not counted, as it decided this was a post hoc multiple comparison artifact. Hmmm.

HOPE was a study of people who already had heart disease going in, or else diabetes with an additional cardiovascular (CV) risk factor. By contrast, WHI was a primary prevention study in mostly-healthy older women drawn from a general population. HOPE was composed of 74% men, whereas the WHI study population was of course 100% women. In keeping with this, CV deaths in HOPE were 6 times the cancer deaths, while in WHI, the cancer deaths were 3 times the CV deaths, a completely opposite result (and not surprising). Finally, the WHI study is 10 times the size: 20,000 women on E and 20,000 on placebo, where as in HOPE-TOO you're looking at 2000 people on E vs. 2000 on placebo. If you want to knock WHI out, you're going to have to come up with 9 times the number of patients as in HOPE-TOO, and make them comparable patients.

If you want to take both study results at face value it suggests you should take vitamin E if you're a typical postmenopausal woman, but not if you're a man who already has heart disease. What is more, the results make sense, as the kinds of sudden death prevented in WHI are the kinds of veinous clotting death seen far more in women than men: half the WHI women smoked, and (of course) half were taking hormone replacement (giving 25% of women doing both, which is 10,000 women in the randomized part-- just the women smoking AND taking hormones in WHI outnumbered the ENTIRE study population of HOPE). More than a quarter of the patients in HOPE died during the study, but overwhelmingly they died of their already-diagnosed coronary artery disease. Vitamin E had no effect on this, and perhaps it did something to make congestive heart failure worse (though this didn't show up in the deaths or MIs, so one supposes it was correctable fairly easily).

In any case you didn't answer my implicit question, which is: what's the point in running very large and expensive studies like WHI if you refuse to believe the results? Doctors still give postmenopausual women Prempro (Provera + Premarin), a drug that has not been removed from the market. Doctors still do not routinely prescribe such women vitamin E. Doctors who give this group Prempro are not called quacks, whereas doctors who do give this group high dose vitamin E are called quacks (MVT quacks, OM quacks, naturopathic quacks, generic quacks). That's bias. The largest study shows a clear result and we have a mechanism. What are you waiting for-- a really expensive prescription form of vitamin E that your health plan or medicare will pay for, as is the case with Lovaza^TM vs. (say) fish oil from Costco? SBHarris 18:15, 18 April 2011 (UTC)

“Traditional” medicine

I see mentions of “traditional medicine”. This is inappropriate. It’s bad enough that we bump fringe theories and fantastical disease models up a few notches by calling them “alternative medicine”. Let’s not drag real medicine down a few notches by qualifying it as “traditional”. That gives a false impression like it’s stuck in time, some kind of dogmatic, ritualistic practice. This would be truer of most alternative therapies than it would be of real medicine. “Traditional medicine” should more appropriately be called “mainstream medicine”, “conventional medicine” or just “medicine”. — TheHerbalGerbil^(TALK|STALK), 11:45, 18 April 2011 (UTC)

Go for it! I usually pull those POV statements out of these articles. OrangeMarlin ^{Talk• Contributions} 16:03, 18 April 2011 (UTC)

"Mainstream medicine" or "medicine" works for me. BGortney (talk) 00:06, 19 April 2011 (UTC)

Actually, I think "mainstream medicine" is probably more appropriate. Using "medicine" would likely bias readers in the other direction by implying that only mainstream theories are legitimate. By definition, new ideas aren't mainstream, and if we stack the deck against them (as a general rule), the only advancements that will be made (accepted) will fit neatly within what's already well understood. History has shown that isn't how it always goes; there are breakthroughs, new ideas, and new views that supersede or replace old ideas, from time to time. BGortney (talk) 00:22, 19 April 2011 (UTC)

Mainstream medicine is no different than traditional medicine. You make these edits without any consensus, then edit war with others. Really, you think this is helpful? Medicine is medicine. PERIOD.OrangeMarlin ^{Talk• Contributions} 22:03, 20 April 2011 (UTC)

The edits are not made with out consensus. Everyone, except you, Orange, sees the illogic of conflating two distinct concepts that already have their own distinct articles. -- cheers, Michael C. Price ^talk 22:02, 20 April 2011 (UTC)

Lead dog song and others have also commented negatively. OrangeMarlin ^{Talk• Contributions} 22:04, 20 April 2011 (UTC)

No, they also did not support the identity of the two distinct concepts. -- cheers, Michael C. Price ^talk 22:06, 20 April 2011 (UTC)

I agree. There's no edit war other than what's due to disruptive editing by, and behavior of, one editor (for which we all deserve an apology, imo), or editing without consensus: Only one editor is still arguing in favor of labeling OM MVT, and we waited several days for a response to requests for supporting RS, which were ignored. Per WP:TALKDONTREVERT, silence implies consensus, and besides, consensus is not unanimity. Also, LeadSongDog's comments/questions suggest he supports alternate wording and clearly sees the distinction between the "set" and "superset". I was well within WP policies/guidelines making my last set of edits. Please, let's leave the attacks/criticism behind and focus on the facts and the article. BGortney (talk) 00:29, 21 April 2011 (UTC)

I've had it with your continued personal attacks.OrangeMarlin ^{Talk• Contributions} 00:41, 21 April 2011 (UTC)

What? I've reviewed WP:NPA and I don't see how what I said can be construed as a 'personal attack'. I defended myself by describing behavior/actions for which solid evidence exists, then requested that we stop with the attacks. I've replied in the new section below. BGortney (talk) 00:56, 21 April 2011 (UTC)

To be clear, it is not that I "support" alternate wording, so much as I consider it an inescapable result of the ongoing pattern of edits here. While I regard the MVT doctrine as an approximate subset of OMM doctrine, I see little difference in a practical sense. They have largely the same group of advocates and practitioners, while being based on much the same shaky foundations. I suggested the compromise wording simply as a way to find a middle ground that would allow the discussion to move beyond unproductive revert warring. Can we approach it in that spirit? LeadSongDog come howl! 17:13, 28 April 2011 (UTC)

Medicine is what doctors do; alternative medicine is interventions that are claimed effective but not proven. Sometimes they are vindicated by research, other times they are not. Medicine incorporates what has been demonstrated to work, while alternative medicine usually handwaves away or special pleads negative results while the actual practice remains unchanging. I would prefer simply "medicine" or failing that "real medicine" but that probably wouldn't play well. Failing that, "mainstream medicine" would be my next preference.

Regarding megavitamin therapy versus orthomolecular medicine, my preference is to state explicitly that some people consider MVT to be a subset of OMM, others consider it synonymous. There seems to be . It depends on what sources we can find for each position, but the best way to deal with a controversy or disagreement is to explore it. Since OMM doesn't really have a governing body or research base with the same weight or standard of care that doctors, via the AMA and other national bodies do, we can't say "OMM is X". There's no central authority to define things since they're not working from an evidence base. WLU (t) (c) Wikipedia's rules:^simple/_complex 18:50, 28 April 2011 (UTC)

Edit warring

Let's come to a conclusion on megavitamin therapy and apparently traditional or mainstream medicine. A let's remember what consensus is. OrangeMarlin ^{Talk• Contributions} 22:03, 20 April 2011 (UTC)

Well the article is protected. Let's talk. To satisfy "me", who isn't the only one here, how about putting some small sentence in the lead about megavitamin therapy as being the precursor or something to OM. Your choice. Your references. But it should be stated that a LOT of people conflate the two, so I really have a hard time seeing your POV on this. OrangeMarlin ^{Talk• Contributions} 22:49, 20 April 2011 (UTC)

My last set of edits mentioned MVT (and all megadose therapies) in the lede. Was that not sufficient? If not, I'll stipulate that OM is mistakenly/erroneously called MVT. Something within a parenthetical? BGortney (talk) 00:40, 21 April 2011 (UTC)

"Orthomolecular Medicine (which is often erroneously referred to as megavitamin therapy) ..." or even

"Orthomolecular Medicine, which is often erroneously referred to as megavitamin therapy, ..." ? BGortney (talk) 00:43, 21 April 2011 (UTC)

LeadSongDog's wording ("Orthomolecular medicine, an extension of megavitamin therapy to include other nutrients ...") would meet with my approval. As regards references, many of those listed in BGortney's Analysis section, above, would be suitable to be used as supporting evidence. Vitaminman (talk) 09:00, 21 April 2011 (UTC)

In selecting refs, quality trumps quantity. Which are the best of the refs? LeadSongDog come howl! 11:59, 21 April 2011 (UTC)

How about saying that OM evolved out of early MVT, and now encompasses it? BGortney (talk) 20:00, 21 April 2011 (UTC)

Which references would you choose to support that particular wording?Vitaminman (talk) 20:16, 21 April 2011 (UTC)

Dr. Braverman explains it well. Orthomolecular Medicine & Megavitamin Therapy: Future and Philosphy. MVT was coined in '52 by Osmond & Hoffer, OM in '68 by Pauling. He also states (as you pointed out) that MVT is now a subcategory of OM. BGortney (talk) 20:46, 21 April 2011 (UTC)

There's what OM is to its advocates, and what OM is to outside parties. For all practical purposes, OM is MVT, per the sources added by OrangeMarlin stated. As the OM sources show, practitioners and advocates of OM see it as many things, depletion, supplementation, exercise, etc., etc., anything in fact that they feel will restore the right amounts of substances.

So what do we settle on? An illustration might help. Look at the lede of our article on Christianity. Then ask an evangelical Christian what Christianity is. They would say it's a relationship with Jesus Christ, a constant state of prayerfulness and communion with the creator. Where is this in the Christianity lede? It's not there, because Christianity, in an encyclopaedia, is defined objectively, not by its most fervent practitioners.

That said, why not keep the old language but add a sentence somewhere about the view of OM advocates? Keepcalmandcarryon (talk) 22:19, 21 April 2011 (UTC)

Again, which sources state that OM is MVT? Can you humor me and list the RS you're referring to here? I still haven't seen any other than the "aka" by ACS (which actually says "megavitmain/megamineral") and a few non-reliable sources found on Google (not posted here) that say that it's "referred to as MVT" (which, as I've said, I'll stipulate to). I don't mean to be difficult, but I haven't seen it yet, and until I have I can't imagine it's right to leave it the way it is.

A few other points:

• I can't see how the illustration using Christianity is relevant. No Christian would disagree with anything in the lede in that article. It's all factually accurate information. In this case, as it stands now, the article modifies the definition of the term itself in a way that introduces an inaccuracy.
• I'm not sure it has anything to do with being a fervent practitioner, but is, again, just simple logic: A!=B. Leaving a logical fallacy in the definition of the term misleads and is simply wrong.
• Even if there were "mainstream" RS that attempted to define it, I don't know why someone "outside" would be allowed to conflate two terms that mean something different to anyone who practices it; that'd introduce inaccuracy and bias, and likely promote confusion. It'd be like allowing one participant in a debate to redefine terms and then requiring the other to use them. No one would ever stand for that.

In my opinion, our job is to inform readers, not perpetuate mistakes (popular or not). Thanks. BGortney (talk) 23:44, 21 April 2011 (UTC)

"For all practical purposes, OM is MVT"?? This is, as I have stated previously, simply absurd. The idea that orthomolecular physicians only use vitamins, and have set aside the use of minerals, amino acids, essential fatty acids and other nutritional components in the treatment of their patients, is ridiculous and bears no relation whatsoever to reality. Vitaminman (talk) 08:45, 22 April 2011 (UTC)

And let's be clear, the sources claimed to show the OM=MVT identity do not show anything of the kind. All they demonstrate is that the phrases are associated with each other. They no more prove identity than the Oranges and Lemons nursery rhyme shows that Oranges are Lemons.-- cheers, Michael C. Price ^talk 10:47, 22 April 2011 (UTC)

Agreed. Vitaminman (talk) 16:02, 22 April 2011 (UTC)

How about saying that OM evolved out of early MVT, and now encompasses it? BGortney (talk) 20:00, 21 April 2011 (UTC) I can live with this. OrangeMarlin ^{Talk• Contributions} 16:06, 22 April 2011 (UTC)

Fine with me. Keepcalmandcarryon (talk) 18:19, 22 April 2011 (UTC)

And make it explicit that OM is broader than MVT. After all, I trust everybody now accepts that not all molecules are vitamins? -- cheers, Michael C. Price ^talk 00:47, 23 April 2011 (UTC)

How about?:

Orthomolecular medicine[1][2] is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing nutrients as supplements, thereby enabling the body to heal.[3][4][5] Proponents believe that non-optimal levels of certain substances often cause health issues beyond simple vitamin deficiency and see balancing them as an integral part of health.[6] Orthomolecular medicine evolved out of early megavitamin therapy, and now encompasses it and a variety of other modalities, including megadose nutrient therapies and mainstream treatments such as pharmaceutical drugs.[Braverman][1]

BGortney (talk) 17:18, 23 April 2011 (UTC)

Not all molecules are nutrients. -- cheers, Michael C. Price ^talk 19:26, 23 April 2011 (UTC)

What do you suggest? BGortney (talk) 23:40, 23 April 2011 (UTC)

The difficulty is that the vast majority of pharmaceuticals are small molecules, yet the intent of OMM is certainly not to encompass evidence based medicine. Some of the descriptions above read as much closer to naturopathy. LeadSongDog come howl! 01:48, 24 April 2011 (UTC)

If there's overlap with naturopathy, there's overlap with naturopathy. Not a problem. Same with evidence based medicine, which all medicine claims to be. -- cheers, Michael C. Price ^talk 09:02, 25 April 2011 (UTC)

Let's not overcomplicate things just as we were starting to agree on the way forward. Here's my proposal, with refs: Orthomolecular medicine is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing nutrients as dietary supplements. It evolved out of early megavitamin therapy and now encompasses it,[7][8] using high doses of nutrients or hormones to prevent and treat a wide variety of conditions. The doses are well above the recommended daily allowance (RDA) and may be used along with special diets and conventional treatment.[9] Vitaminman (talk) 09:05, 24 April 2011 (UTC)

Good grief, is there some reason why the word "molecule" is shunned? Or replace "nutrients or hormones" with "substances", if that is just too radical. -- cheers, Michael C. Price ^talk 09:36, 24 April 2011 (UTC)

"Molecule" isn't specific enough. For example, Ununseptium and Ununoctium are also molecules, but I'm not aware of any orthomolecular physicians using them to treat patients!! Vitaminman (talk) 09:56, 24 April 2011 (UTC)

I give up. -- cheers, Michael C. Price ^talk 09:59, 24 April 2011 (UTC)

Me too - those are elements, not molecules. :P MastCell ^Talk 03:13, 25 April 2011 (UTC)

The pedantic nature of this holiday-weekend discussion aside, and at the risk of falling prey to this contagious problem myself, are you saying that "molecule" or "substance" would be specific enough for a definition relating to micronutrients and hormones? Surely, for an encyclopedic article, wouldn't it be preferable to narrow down which particular classes of molecules or substances we are referring to? Vitaminman (talk) 08:31, 25 April 2011 (UTC)

Of course "molecule" or "substance" would be specific enough. Molecule was what Pauling said. Why are we (you) trying to redefine it? There is no utility to redefining it, or over specifying it. -- cheers, Michael C. Price ^talk 08:58, 25 April 2011 (UTC)

Then would you care to provide us with your proposed wording, with supporting refs? Vitaminman (talk) 09:52, 25 April 2011 (UTC)

I haven't supplied references, since you can find refs to push any POV. Let's sort out the text using logic first.

Orthomolecular medicine is broadening of megavitamin therapy to include all substances, not just vitamins. Normally classified as a form of complementary and alternative medicine, it seeks to maintain health and prevent or treat diseases by optimizing intakes, often - but not always - by means of nutritional supplements or dietary modification.

The term "orthomolecular" was coined by two-time Nobel laureate and chemist Linus Pauling to mean "the right molecules in the right amounts" (ortho is Greek for "right"); thus orthomolecular medicine focuses on using the right molecules in the right amounts for the individual. Practitioners often recommend a specific form of therapy called megavitamin therapy which calls for doses of nutrients much larger than those recommended by traditional medical authorities. The term is not used in traditional medicine, where clinical use of specific nutrients is considered a form of chemoprevention (to prevent or delay development of disease) or chemotherapy (to treat an existing condition).

-- cheers, Michael C. Price ^talk 12:14, 25 April 2011 (UTC)

Hope everyone had a good holiday. OM isn't just (mega-)dosing, as it sometimes involves reductions. How about:

Orthomolecular medicine[1][2] is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements.[3][4][5] Proponents believe that non-optimal levels of certain substances often cause health issues beyond simple deficiency and see balancing them as an integral part of health.[6] Orthomolecular medicine evolved out of early megavitamin therapy, and now encompasses it and a variety of other treatment modalities, including dietary restriction, megadose therapies (using both nutrients and other substances), and mainstream pharmaceutical drugs.[Braverman][1]

The term "orthomolecular" was coined by two-time Nobel laureate and chemist Linus Pauling to mean "the right molecules in the right amounts" (ortho is Greek for "right"); thus orthomolecular medicine focuses on using the right molecules in the right amounts for the individual.

I agree with Michael's earlier suggestion to leave the commentary about MVT out of the opening section, so this would be it. Thoughts? BGortney (talk) 19:23, 25 April 2011 (UTC)

References are needed for the second paragraph. Whilst I personally accept the validity of these statements, the reality is that, without appropriate citations, non-adherence to WP:NOR and WP:RS will likely be cited by some editors as a reason for not accepting this. Vitaminman (talk) 23:24, 26 April 2011 (UTC)

Agreed. I'll put them in when protection expires and we can iterate as normal from there. BGortney (talk) 19:41, 27 April 2011 (UTC)

I've removed "two time nobel laureate", which is a little close to "brilliant genius you would be a fool to argue with because he's so brilliant therefore all his ideas must be right". Or WP:PEACOCK if you prefer. One of his prizes was for peace, and it's not like his "vitamin C can cure everything" theory panned out. WLU (t) (c) Wikipedia's rules:^simple/_complex 01:09, 28 April 2011 (UTC)

Perhaps that the Nobel committee recognized him twice is less meaningful now that they've recognized Barack Obama (and others) for doing nothing, and I actually agree that the wording encourages the reader to favorably weight his views [perhaps unfairly]. But should we also remove references to credentials of proponents of well-accepted mainstream theories/treatments, or all references to Nobels? And pardon me for saying - I'm sure you're a nice person - but your anti-alternative bias is showing (he didn't actually say vitamin C would cure everything, and I'm sure you know that). Anyway, I'll update the article with what was discussed previously. BGortney (talk) 02:23, 28 April 2011 (UTC)

I'm not a nice person, thanks, but I do know a peacock word when I see one. His Laureate credentials are not relevant here, since he was promoting ideas well past what the evidence base supported even then, let alone now, and ideas outside his expertise. It's like citing Einstein's opinion on haberdashery - sure, he was a brilliant physicist. But would you let him sew you a suit? Criticisms, particularly criticisms of fringe theories by mainstream authorities, can sometimes benefit from noting the expertise and qualifications of the critic as this gives due weight to the mainstream opinion. Are there any other credentials in the page? I've searched for PhD, doctor, Dr. and found none. WLU (t) (c) Wikipedia's rules:^simple/_complex 03:06, 28 April 2011 (UTC)

Yes, I'd let Einstein make me a suit. I assume he'd do a good job, and, really.. it'd be my Einstein Suit. Who wouldn't want one?

Anyway, as I said, I understand your point; it was clear, and I actually agree with you. But my point is that we shouldn't give undue weight (by credentialing) to proponents of 'mainstream' views, either. The mainstream is often dead wrong: we're going backwards wrt cancer (morbidity and mortality are increasing) .. iatrogenic injury and death are meaningful and significant .. pharmaceutical drugs are often improperly tested, rushed to market, widely prescribed, and then create more problems than they solve in the name of profit (e.g. statins do more harm than good) .. and I could go on and on. I'm sure you know (nice person or not) that even a large number of people saying something doesn't make it so. Popular delusions & the madness of crowds, groupthink, herd behavior, and all of that. Credentialing (and therefore weighting) someone 'mainstream' is just as improper as weighting someone outside it. But, this isn't a forum. I'm not sure if there are other credentials referenced in the article; I was speaking generally. 'Evening. BGortney (talk) 03:49, 28 April 2011 (UTC)

Good job Bgortney. Good job. OrangeMarlin ^{Talk• Contributions} 04:40, 28 April 2011 (UTC)

We should give due weight to the majority opinion, for instance by including the information that some supplements are harmful in the lead (which I've replaced). We should note that megavitamin therapy is where orthomolecular medicine originated, and that it's still an approach used. Your claims that the majority is dead wrong is for one thing your opinion, and for another thing irrelevant. We document the majority opinion, we don't judge it, we don't try to promote the "alternative", we don't try to predict how it will change and we don't criticize drugs and pretend that justifies unsubstanitated megadose or other unsubstantiated approaches. Credentialing can be important because we are attempting to write a neutral article; please read WP:NPOV carefully as "neutral" does not mean "fair", "balanced" or "from the perspective of the proponents". "Neutral" means "from the mainstream perspective" and fringe theories like orthomolecular medicine should be placed within their proper context in relation to real, proven medicine. That means we discuss the approach used, the main proponents, but give most of our weight and generally the last word to how actual doctors view the approach.

Morbidity and mortality for cancer is probably increasing because the North American population is living so much longer and dying far less of heart disease and infectious agents (i.e. because of the incredible successes of real medicine). I could go on and on, but it would be easier to note that this page is about orthomolecular medicine, not the alleged failings of real medicine. WLU (t) (c) Wikipedia's rules:^simple/_complex 11:36, 28 April 2011 (UTC)

Ralph W. Moss (science writer)

Please fix the link to Ralph W. Moss (science writer) instead of the other Moss.

I'll get it when the page is unprotected if someone doesn't beat me to it. BGortney (talk) 19:26, 25 April 2011 (UTC)

Fixed, unless there were more. You can also use {{editprotected}}. - 2/0 (cont.) 17:26, 26 April 2011 (UTC)

Scope

I don't like the laundry list in "scope". Rather than listing every single condition OM has been promoted for, it makes more sense to have a general statement about it being promoted as effective for a variety of conditions while only discussing those it has specifically found to be effective, or ineffective in treating. WLU (t) (c) Wikipedia's rules:^simple/_complex 03:09, 28 April 2011 (UTC)

I agree. Was thinking the same thing. BGortney (talk) 04:07, 28 April 2011 (UTC)

POV

This article has some serious "BLP" issues with facts and POV. Like an embarrassment for WP.--TheNautilus (talk) 20:06, 31 January 2012 (UTC)

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)

Cassileth's false statement, again

Cassileth, with a PhD in Sociology, doesn't repeat her prior statement from the first edition, which is nakedly false, starting with prescription niacin. It is at best an obsolete statement, since 1955 much less 1999, made by an administrative/political person with non-technical degree credentials.--TheNautilus (talk) 20:00, 31 January 2012 (UTC)

still waiting on RS Pss

Still waiting for an RS on Pseudosci, for such an easy categorization.--TheNautilus (talk) 20:03, 31 January 2012 (UTC)

vitamin D3

Vitamin D3 is an example of a vitamin that may exceed 5xRDA and 10xRDA definition of OMM, especially for the old 200iu limit. It should be restored for balance.--TheNautilus (talk) 20:10, 31 January 2012 (UTC)

MTHFR

(1st wiki edit, sorry for clumsiness).

POV: this article mostly casts doubt on the concept of individualized nutrition and would lead someone to think the field is all quackery. I would prefer it to be a bit more open-minded to the possibility that there are cases where individuals need tailored supplements. The digestive system and the immune system are deeply interconnecting, and future research may identify more valid situations. This article casts the entire topic in a dubious light.

My personal case: I have Lyme disease and a number of other tick-borne infections. People with Lyme very often have digestive issues that can create difficiencies that require specific supplementation. Lyme doctors are aware that those patients with serious Lyme are more likely to have certain gene variants that interfere with the liver's ability to dispose of normal toxins (heavy metals, etc.)

On a hunch, I requested a gene test for MTHFR. There are two primary variants that can contribute to disease. I have the variant that reduces my ability to convert Folic Acid to Methyltetrahydrofolate. Women with this variant have a significantly higher risk of miscarriage, as insufficient folate leads to neural tube defects, spina bifida, etc. In such cases, a tailored dose of folic acid or Methyltetrahydrofolate can help achieve a successful pregnancy.

MTHFR defects can also lead to a wide range of other health issues, including cardiovascular disease, depression/anxiety, etc. These conditions are sequelae to the insufficient level of Methyltetrahydrofolate: there are a number of processes that require chemical reactions based on available methyl molecules, and without the methyl from the folic acid, they can't happen. This can lead to hyperhomocystinemia and liver incompetence. The liver requires glutathione to release toxins; without methyl, you can't produce glutathione; without glutathione, you can get heavy metal build-up, which is implicated in some neurological conditions such as Autism, schizophrenia, and depression/anxiety.

The point is that at least one non-rare genetic variation in the MTHFR gene can be compensated for by tailored nutrition, which may result in improved neuro/psychological condition. So while the ideas that started orthomolecular nutrition may be unsound or unproven, the mechanism is valid. Future research may reveal other specific gene variants that may need different supplementation. Cassiebabe (talk) 02:23, 23 March 2012 (UTC)

NPOV dispute

Several sources that are cited in this article are erroneous and misleading references, since they do not support the claim stated in the article.

Example 1: "…and there is research suggesting that certain nutritional supplements are harmful [14][15][16]…"

• Source [14] does NOT suggest this. They found contradicting findings during their literature studies, and conclude that "the present evidence is insufficient to recommend either for or against the use of MVMs."
• Source [15] does not say this either. Instead, in its conclusion section it says: "Evidence is insufficient to prove the presence or absence of benefits from use of multivitamin and mineral supplements to prevent cancer and chronic disease."
• Source [16] concludes: "We found no evidence to support antioxidant supplements for primary or secondary prevention." For several vitamins, effects are marginally significant, and the conclusion states: "Vitamin A, beta-carotene, and vitamin E may increase mortality."

Example 2: "...with several specific vitamin therapies linked to increased risk of cancer, heart disease, and death.[17][18][19]"

• I would opt to change "cancer" into "lung cancer", since this was the only type of cancer that vitamin E was shown to significantly affect, in [17].
• [19] is a source-to-a-source (BBC news article), so I would suggest to change that to the actual source: "Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality" (http://www.annals.org/content/142/1/37.short)

Moreover, almost all references that in the article are said to attack "vitamins and other nutrients" actually only attack an excessive dose of vitamin E. Hence the specific section "Example: vitamin E." This gives a biased view of orthomolecular practice as a whole.

I wanted to discuss these things first before changing anything. I hope you all agree with these points. If so, could they please be changed, or could some Dubious markers be added?

86.31.82.84 (talk) 21:31, 28 April 2012 (UTC)

You can use the {{Failed verification}} tag to express your concerns during discussion. SÆdon^talk 22:04, 28 April 2012 (UTC)

Fully agree with your points, 86.31.82.84. Vitaminman (talk) 08:08, 29 April 2012 (UTC)

These studies don't "attack" vitamin supplementation; they study it to try to actually find out whether it works or not, although I recognize that applying any sort of scientific scrutiny to these sorts of therapies is often perceived as an "attack". I also don't understand your parsing of the sources. The three you cite (14, 15, and 16) clearly support the article as written:

• PMID 17332802 (ref 14): "several other studies also provide disturbing evidence of risk, such as increased lung cancer risk with beta-carotene use among smokers."
• Ref 15: you're correct, the focus there is on the poor quality of the evidence base as a whole rather than on potential harms.
• PMID 18425980 (ref 16): "Vitamin A, beta-carotene, and vitamin E may increase mortality." The 2012 update (PMID 22419320, which we should be referencing instead) re-states this more forcefully: "Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A."

So I don't see any support for the reductive gloss you want to put on these sources - they seem quite clear, for the most part, in supporting the language currently in the article. MastCell ^Talk 03:32, 30 April 2012 (UTC)

Another update needed is for PMID 21735411. LeadSongDog come howl! 04:20, 30 April 2012 (UTC)

Dubious wording

I have undone this because:

• Replacing "increased risk of death" with " all-cause mortality risk difference" looks like a cunning way of using sciency-looking words whilst hiding the central fact from readers: That more people die, rather than fewer.
• The bit around Ernst and Singh looks like special pleading. Frame Ernst and Singh as though it's just an opinion, then say - oh noes! - the hair analysis example is just an example.

Pottinger's cats, please stop this whitewashing. bobrayner (talk) 11:18, 19 January 2013 (UTC)

Yeah, that wording is obfuscating the source. Casliber (talk · contribs) 14:05, 19 January 2013 (UTC)

The Ernst and Singh statement is erroneous, and does not reflect the content of Hoffer's text - the wording has been changed as a compromise.Pottinger's cats (talk) 13:43, 20 January 2013 (UTC)

This isn't a "compromise", it's just more whitewashing. bobrayner (talk) 14:24, 20 January 2013 (UTC)

It's an inclusion of meta-analyses that controvert the meta-analyses in this article. It's not whitewashing.Pottinger's cats (talk) 14:38, 20 January 2013 (UTC)

First, the only mention of the word "hair analysis" in Hoffer's text refers to testing for heavy metal toxicity[10], and this is not a fringe practice: http://cfpub.epa.gov/si/si_public_record_Report.cfm?dirEntryId=45357&CFID=112265176&CFTOKEN=24229651&jsessionid=cc30c5910d452be802487f54312560762d70 Second, I added meta-analyses that incorporate the latest research, and controvert the 3 here. I used the wording requested.Pottinger's cats (talk) 02:21, 22 January 2013 (UTC)

New meta-analyses

I added the following text: http://en.wikipedia.org/w/index.php?title=Orthomolecular_medicine&diff=534265968&oldid=534264205

This is apparently against consensus, according to Mathsci, though I changed the wording to comply with requests.

What justification is there for not using this?Pottinger's cats (talk) 04:07, 22 January 2013 (UTC)

It is a ridiculous amount of detail. Unless there is reason to think the earlier publications were improperly omitted from the latest, best ones we would simply state the finding of these latest. That would be PMID 23255568 and the 2012 update to the Cochrane review. I would restate the findings of PMID 23255568 in direct terms such as "Overall, combined vitamin and mineral supplements had little or no effect on mortality rates." If the reader wants the details of the study, they can read it themselves, that's why we cite it. LeadSongDog come howl! 14:22, 22 January 2013 (UTC)

Am I allowed to use these sources and the above source correcting the hair analysis comment? User:Bobrayner states that I am "abusing sources" - I feel that his reversions to my edits in this case are unwarranted. I feel that my edits are entirely appropriate, as they directly controvert the sources given thus far, and this is explicit in their abstracts. Pottinger's cats (talk) 02:34, 23 January 2013 (UTC)

We'd need a reliable source that comments on the omission of "hair analysis" from that text. Making such a comment without such a source is clearly synthesis, or wp:UNDUE at best. LeadSongDog come howl! 03:23, 23 January 2013 (UTC)

You're right - though the text does not mention hair analysis, per WP:SYN, we can only refute secondary sources with secondary sources.Pottinger's cats (talk) 03:56, 23 January 2013 (UTC)

This is what I would state for a revision to the "Example: Vitamin E" section:

Two meta-analyses have produced contradictory results on vitamin E and mortality rates. One, in 2005, reported that >=400 IU/d increased mortality rates. A 2011 meta-analysis controverted this, stating that supplementation with vitamin E appears to have no effect on all-cause mortality at doses up to 5,500 IU/d. A 2012 Cochrane review reported that Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A, though overall, combined vitamin and mineral supplements had no effect on mortality rates.

Pottinger's cats (talk) 05:06, 23 January 2013 (UTC)

I would like to add - for the record, that the Cochrane review is suspect because of the following: http://www.mdpi.com/2072-6643/2/9/929 Pottinger's cats (talk) 05:16, 23 January 2013 (UTC)

That would seem to refer to the 2008 Cochrane review, not the 2012 update. LeadSongDog come howl! 06:39, 23 January 2013 (UTC)

Another review would have to be done on this update then. But if it (the Cochrane review) incorporates data from the previous, it is relevant.

I have skepticism about these claims for 2 justifiable reasons though:

1) In a 2008 review Does pharmaceutical advertising affect journal publication about dietary supplements?, Kemper, et al., report that "Journals with the most pharmads published no clinical trials or cohort studies about DS. The percentage of major articles concluding that DS were unsafe was 4% in journals with fewest and 67% among those with the most pharmads (P = 0.02). The percentage of articles concluding that DS were ineffective was 50% higher among journals with more than among those with fewer pharmads (P = 0.4).": http://www.biomedcentral.com/1472-6882/8/11

2) Morbidity claims are also inconsistent with real world data. Data on fatalities comes from the American Association of Poison Control Centers. In determining cause of death, AAPCC uses a 6-point scale called Relative Contribution to Fatality (RCF). A rating of 1 means "Undoubtedly Responsible"; 2 means "Probably Responsible"; 3 means "Contributory"; 4 means "Probably Not Responsible"; 5 means "Clearly not responsible (and Not Contributory)"; 6 means "Unknown - In the opinion of the Case Review Team the Clinical Case Evidence was insufficient to impute or refute a causative relationship for the SUBSTANCES in this death." (see p. 832 0f the 2006 document, below, per WP:V - to verify my citations).

The American Association of Poison Control Centers (AAPCC) attributes annual deaths to vitamins as (for all of these, refer to the page numbers of the document, not the pdf). If I am mistaken in my citations, feel free to correct me:

1. 2010: zero - see p. 139: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/2010_NPDS_Annual_Report.pdf
2. 2009: zero - see p. 1148: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/NPDS_Annual_Report_2009_1.pdf
3. 2008: zero - see p. 1053: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/NPDS_Annual_Report_2008_1.pdf
4. 2007: zero - see p. 1028: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/2007annualreport.pdf
5. 2006: one - see p. 890 - for this, RCF is 4 - probably not responsible - see p. 871 - and in this, the vitamin is of "unknown" category (again see p. 890): https://aapcc.s3.amazonaws.com/pdfs/annual_reports/2006_Annual_Report_Final.pdf
6. 2005: one - see p. 915 - RCF is not given - again, of "unknown" category: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/Clin-Tox_AAPCC_2005_Annual_Report.pdf
7. 2004: three - see p. 653 - RCF is not given - one from a multi-vitamin with iron, one from vitamin D, and one from Viamin E - but since RCF is not given, we cannot make any meaningful statements about this: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/AJEM_-_AAPCC_Annual_Report_2004.pdf
8. 2003: four - see p . 392 - RCF is not given - this is of a multi-vitamin with iron, vitamin B6, vitamin c, and a multi-vitamin with iron - but since RCF is not given, we cannot make any meaningful statements about this: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/AJEM_-_AAPCC_Annual_Report_2003.pdf
9. 2002: one - see p. 410 - RCF is not given - vitamin E - but since RCF is not given, we cannot make any meaningful statements about this: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/AJEM_-_AAPCC_Annual_Report_2002.pdf
10. 2001: zero - see p. 443: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/NPDS_Annual_Report_2001.pdf
11. 2000: zero - see p. 387: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/NPDS_Annual_Report_2000.pdf
12. 1999: two - see p. 566 - from multivitamin with iron - RCF is not given - again, RCF is not given, so we cannot make any meaningful statements about this: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/AJEM_-_AAPCC_Annual_Report_1999.pdf

Pottinger's cats (talk) 08:01, 23 January 2013 (UTC)

Why not ask the corresponding author(s) of the published reviews to address it? It's certainly a level of detail far beyond what a group of pseudonymous wikipedians can address. We don't do analysis, we simply report what analysis other experts have published, based on the best available sources. LeadSongDog come howl! 14:04, 23 January 2013 (UTC)

It appears that my citations of the 4 meta-analyses given above are acceptable. As such, I have changed the article to reflect that.Pottinger's cats (talk) 02:45, 24 January 2013 (UTC)

You've entirely missed the point. They are not. Your interpretation of a bunch of outdated meta-analyses cannot be substituted for or used to challenge a more-current systematic review. The key finding of PMID 22419320 was "We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing." That review had access to all the other sources you are pushing to include, so they are not needed. LeadSongDog come howl! 05:38, 24 January 2013 (UTC)

Agree with LeadSongDog. We don't use older meta-analysis that rebuts a 2008 study when a newer 2012 study has been published. Yobol (talk) 15:55, 24 January 2013 (UTC)

proposed revision

I would like to replace the use in AIDS section in accordance with the criticisms noted here: http://en.wikipedia.org/wiki/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)

sources

• Paul M. Insel, R. Elaine Turner, Don Ross Nutrition, Volume 1 [11]
• W. Edward Craighead, Charles B. Nemeroff The Corsini Encyclopedia of Psychology and Behavioral Science, Volume 3 [12]
• John W. Jacobson, Richard M. Foxx, James Anton Mulick Controversial therapies for developmental disabilities: fad, fashion, and science in professional practice [13]
• Dónal O'Mathúna Alternative Medicine [14]
• 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)

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 [SD] age, 64.3 [9.2] 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 Wikipedia.

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 ^{talk|contribs|COI} 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 ^{talk|contribs|COI} 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. -- [ UseTheCommandLine ~/talk ]# ▄ 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 ^Talk 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 Wikipedia 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: [15]. 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. -- [ UseTheCommandLine ~/talk ]# ▄ 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? -- [ UseTheCommandLine ~/talk ]# ▄ 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)

References

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. James^x12345 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 ^{talk|contribs|COI} 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. James^x12345 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: [16]. 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 ^Talk 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 ^{talk|contribs|COI} 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 ^Talk 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 ^Talk 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)

getting a little bit NOTFORUMy

The book will never be shut. There is no combination of negative trials that will convince the hardcore Vitamin C advocates, because their views are no longer rational and thus not open to reason. For any negative trial, they will respond that the trial tested the wrong dose of vitamin C, or the wrong route of administration, or the wrong synergistic chemotherapy... I think you've seen as much on this talkpage. MastCell Talk 23:02, 17 September 2013 (UTC) While there's certainly a large contingent who are completely irrational, I think Mark Levine and his team out at Bethesda can probably be convinced. It seems he's staked a fair part of his career on this topic. Also found another Phase I trial along the lines of Monti (Welsh et al 2013) and the Puerto Rico trial by (Riordan et al 2005) which was by the indubitably credulous proponent himself, Hugh D. Riordan. Regardless of his faith, he apparently had enough integrity to report that in nearly all of the 24 cases there was just progression. II | (t - c) 04:10, 18 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 [26], [27], [28], [29], [30], [31].

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 [20]."

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 ^Talk 03:27, 24 September 2013 (UTC)

I don't think the article could be modified because of this, but I just noticed some errors in interpretation. As a correction, see what happens when we consider those who actually completed the study, from the article "By RECIST 1.0 criteria, 7 patients had stable disease and 2 patients had progressive disease (non-responders)."- also, see this figure regarding response, the tumor size decreased in many cases: http://journals.plos.org/plosone/article/figure/image?size=medium&id=info:doi/10.1371/journal.pone.0029794.g003Ortho5 (talk) 18:53, 23 January 2017 (UTC)