Talk:Orthomolecular medicine/Archive 4

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This is an archive of past discussions. Do not edit the contents of this page. If you wish to start a new discussion or revive an old one, please do so on the current talk page.

Contents 1 Paradigm 2 Preferred vitamin E amd controlling for other vitamin levels 3 POV edits by Nautilus 4 A gentle suggestion 5 "Frequent" use of OM 6 A few things... 7 Preferred vitamin E and controlling for other vitamin levels 7.1 B-carotene & "vitamin E" 8 OR

Paradigm

Previous discussions: [1][2] As I said before, [3] I am looking at the "conceptual framework" and "pattern of thought and ideas" version of "paradigm" to express an important descriptive, introductory element about orthomed.

• Compact Oxford English Dictionary: "2 a conceptual model underlying the theories and practice of a scientific subject."
• Merriam-Webster's Online Dictionary, 10th Edition: "3 : a philosophical and theoretical framework of a scientific school or discipline within which theories, laws, and generalizations and the experiments performed in support of them are formulated; broadly : a philosophical or theoretical framework of any kind"
• Wiktionary: "3. A way of thinking, perceiving or approaching work in some context"
• The American Heritage® Dictionary of the English Language: "3. A set of assumptions, concepts, values, and practices that constitutes a way of viewing reality for the community that shares them, especially in an intellectual discipline."
• Encarta: "4. relationship of ideas to one another: in the philosophy of science, a generally accepted model of how ideas relate to one another, forming a conceptual framework within which scientific research is carried out"

It is important to describe the subject and orthomed is more than some mere aberration of medical practice, it has a large philosophical component that its critics here wish to deprecate, such as the old prejudicial "cult" quote[4] which indirectly acknowledges the philosophical component in a very negative way. Words like "theory" or "hypothesis" certanly are too specific (there are at least many hypotheses in orthomed - in fact, J of Ortho Med's closest cousin in Medline is Medical Hypotheses, with ongoing streams of hypotheses), a "framework of hypotheses and thought pattern" is awkward and still deficient. I think that the average, educated Wiki reader understands from the context that paradigm here *does not* mean: 1. "One that serves as a pattern or model." 2. "an example of a conjugation or declension showing a word in all its inflectional forms" I am searching for succinct wording that conveys this element.

AGF on your comment about POV, I suspect one definition that might fit your concerns if one assumes that your reading of "paradigm" assumes or associates "Medicine" alone rather than "orthomolecular medicine" is: "the generally accepted perspective of a particular discipline at a given time" which is a little narrow and presumptive in reading for this context. A solution might be to briefly clarify that the orthomolecular paradigm separates or extends from the conventional medicine field in the overlap areas and / or the philosophical / experimental elements. (I might say "alternative paradigm" but that would be confusing since orthomed overlaps conventional med whether conventional medicine likes to recognize this or not)

"...paradigm is more or less seem as a byword for pseudoscience). Jefffire 14:37, 19 August 2006" Although I would agree that in the late 80's "paradigm" became a trendy word to describe every little hypothesis and brain fart d'jour, it is still a good and useful word that is difficult to replace here.

"Could you provide evidence of this widely accepted paradigm shift? Addhoc 10:36, 19 August 2006" No such claim to have won the hearts and minds of the population, the scientific community or medical community is made. Rather orthomed is a conceptual framework that adds to and challenges conventional medicine as it exists today. Although there are long running "signature" conflicts, such as vitamins C & E, orthomed preparations are progressing more unobtrusively in areas not so clearly identified or labelled as OM related. See the definitons discussion above about medicine vs orthomolecular medicine assoc'd with paradigm.

I recognize that some editors here may not be comfortable with "paradigm" but orthomolecular medicine has Pauling's organizing principle that he identified as an idea (before paradigm's popular use) and guides its philosophic, scientific and medical directions. The current introduction without "paradigm" shortchanges this descriptive element.--TheNautilus 21:10, 6 September 2006 (UTC)

Preferred vitamin E amd controlling for other vitamin levels

This edit [5] raised the issue that authoritative studies with the preferred vitamin E have not been done. However, it then goes on to comment about controlling for "bile, pancreatic function, certain specific heart problems and risk factors, blood levels and cofactors (vitamins C, D3, K1, K2, selenium, co-enzyme Q10, etc.) in the common orthomolecular range, 600-3200 IU alpha tocopherol plus 25%-50% by weight of other R,R,R tocopherols." Controlling for these vitamin levels seems excessive and not routinely done in clinical trials. Furthermore, it's not clear if controlling for these levels actually has a medical basis. (Of course you need to control for heart disease and other comorbidities). Andrew73 12:33, 7 September 2006 (UTC)

Sorry Andrew, I'll have to get back later on this discussion.--TheNautilus 16:52, 8 September 2006 (UTC)

Current discussion moved & restarted more chronologically.--TheNautilus 00:44, 24 October 2006 (UTC)

POV edits by Nautilus

I find it very disturbing that, after a month where consensus was reached on how to make what was an extraordinarily biased article NPOV, Nautilus waits a few weeks for the controversy to die down, and then reverts everything back to a POV version over the Labor Day weekend. If Nautilus persists in refusing to adhere to NPOV, I will escalate within the appropriate Wikipedia rules. -- Cri du canard 10:39, 8 September 2006 (UTC)

'Canard, you show the extraordinary bias, with the QW site as your primary if not sole source of "insight and knowledge". You have unfairly criticized, attacked and mischaracterized my editing from the start e.g. I did not drive DocJohnny off as you allege - actually I invited his opinion: "question on orthomolecular med POV"^EditSummary - "So what is DocJohnny's take on orthomolecular medicine?"[6], although I got more than requested! DocJohnny addressed me point by point on issues in a highly skptical, persistant but polite, rational manner when directly challenged - *urging me to continue editing* "Please continue to edit so we can achieve a consensus on NPOV. Despite our differences in opinion, I feel that is possible "...[7], a distant fond memory here.

No real consensus was reached in August, I was absent on other things and decided to see how POV you & the ps/QW gang would go here anyway before attempting to achieve an encyclopedic article again with expanded material. You seem to have successfully driven off Linas, an new independent view & ignored Dr Harris, a real MD. MC Price seems to be currently absent. Your twisted legalistic threats are primarily of wasting everybody's time from the start. Although I did not have much time to dissect your continued "right thinking" tirades against me and others after your highly disparaging "pseudosci" labelling campaign[8][9] was initiated, I suspect independent, informed admins might have something to say to you. Your edits show little familiarity with the primary sources & rationale of orthomed but rather recycle the QW attack site material which is provably highly biased, e.g. QW "disproving" daily "high doses" of vitamin C for colds[10] with laughably small amounts of vitamin C / ascorbic acid that don't even rise to the initial dose for the first 60 seconds (up to 8 grams), much less 20-30 minute repeats until bowel tolerance dictates the subsequent dosing schedule, typically 40-100 grams/24 hr divided into 0.1 - 2 hr intervals, phasing down as one's condition improves and bowel tolerance to AA declines. Kidney stones?[11] many people have persistant urinary non oxalate sediment that is easily reversible with AA (may be seen at home for the inquiring scientists, since 1946[12]) and Klenner addressed the oxalate issue pretty well by 1971[13].

The introduction's revert with the "mainblame game" groups list are disproportionate detail, some by groups with their own clear, citeable biases such as APA & ACS, that seem to be calculated to "poison" the reader's mind. Unacceptable - "unsubstantiated claims, lack of proven benefits, and serious toxic effects" - stated in a highly misleading and highly POV manner. Just because AAP cites a toxicity concern, it is realistically contradicted by decades of evidence in the poison control data that include non-orthomolecular exposure levels (e.g. suicide attempts, less orthomolecular versions of formulas abusively used, that clearly shown almost every pharmaceutical as much, much worse). Pauling's lifelong battle with colds is cited[14] by a fervent QW supporter that has no scientific measure of Pauling's aging, health problems and improvement, in a tabloid sourced manner (it is hearsay). Pauling was clearly worried about his wellbeing in the 1960s and stated he, the primary source, on balance, felt *much* better with vitamin C, enough to pursue it scientifically for 25+ years more. For a man most likely fated to die in the 1940s by conventional medical reckoning[15], Pauling's resorts to unconventional, biochemically based health solutions seems propitious, rather than with such derision anyway.--TheNautilus 19:42, 8 September 2006 (UTC)

A gentle suggestion

I wonder if you'd mind me making a gentle suggestion here. I can't stay but would prefer to see some harmony here, although maybe I'll upset everyone. I think it is sometimes a fair criticism of "pro science" cases that they (rightly) demand high levels of evidence for non standard views, but do not display clearly the same standards when describing their case. I don't think there's any excuse for that in the end; good V RS peer reviewed sources, available for inspection (ideally online) and rigorous citation of them should be a hallmark of the "mainstream" approach. Now the information in QW may be reliable; I would expect it to be, but it is not clearly a peer reviewed source; if there are better sources they should be used, if there are not better sources, maybe there needs to be some reflection on why not by the editors. On the OM side, some information is referenced to non peer reviewed sources. I can understand why this might be unavoidable. If information is included from sources that are not highest V RS, maybe this can be accomodated by explicitly conceding (coolly rather than provocatively) the weaker nature of the source. The attribution of references to potentially contentious points does need checking carefully in places. For example "because of unsubstantiated claims, lack of proven benefits, and serious toxic effects.[7][6][5][9][10]", I confess I haven't checked, but do all of these references support all of these points? It is not clear to me that [9] does for example, but your wording implies that all the named organisations endorse all the stated claims; you didn't intend it, but this sentence inadvertently expresses an inference beyond the stated evidence, and from the other side accordingly looks like a blatant POV distortion. Don't you really mean "risks of" serious toxic effects? Are you happy with the quality of these sources - I would prefer sources that are available online for verification, at least in abstract form, and some seem distinctly more authoritative as sources than others. I think that some self-critical reflection might help; the science case can, and I think should, be made much stronger by close and rigorous adherence to the standards that it would wish the altmed case to adhere to. OK it might seem pedantic; but precision and close justification builds the best cases. Where the evidence leads I'm in no position to prejudge; I know where I expect it to go, but it goes where it goes, and in the end it's for us just to display the best evidence and most notable opinions clearly, and allow the reader to judge.Gleng 23:04, 14 September 2006 (UTC)

Thanks, Gleng this point is where my edits are headed in the body with the moved material, after a succinct Intro summary. The BC Cancer Agency ref [6] I have criticized at length here before, it is discredited, with more available. The main, recycled underlying pediatric ref, [10], criticizes megavitamins' lack of validated efficacy and then jumps w/o reference to ("mega")overdoses generally. It *does not* address orthomolecular overdoses of vitamins & minerals (e.g. orthomeds indiscriminately pushing overdosed iron and copper supplementation which they consider iron a conditional male poison for 1/9 of the population & copper a frequent environmental problem??? I think not, this is a problem of conventional supplements, megavitamins usually offer no/low iron & copper versions.) but rather misuses (accidental or otherwise) and more medical/harmaceutical versions like [10] alluded to vitamin analogues and pregnancy. You know, vitamin Accutane ;>-TheNautilus 23:34, 14 September 2006 (UTC)

"Frequent" use of OM

I see the article has been reverted to read:

Orthomolecular type treatments have frequently been experimentally or empirically introduced by physicians with advanced scientific backgrounds when conventional medical treatments offered neither solution[11][12] nor hope.[13][14]

The references provided do not back this up. OM has not been "frequently" employed by physicians; the references are from a handful of physicians outside the medical mainstream. I'm removing the "frequently" unless there is some evidence cited that these treatments are, in fact, frequently used by physicians. Also, I'm removing "with advanced scientific backgrounds". The cited physicians have the typical training and credentials of a physician anywhere; to insist that they have "advanced scientific backgrounds" is redundant and sounds like an appeal to authority. MastCell 23:31, 22 September 2006 (UTC)

Yes, I corrected it. Your interpretation of "frequently" here is a total misread, "frequently introduced" or "frequently discovered" is the sense of the usage, i.e. Hoffer (PhD/MD) & niacin, William Kaufman (MD/PhD) and niacinamide, Klenner (near PhD, 1932, MD) on IV ascorbate, and most of the orthomolecular treatment discoverers were in no way typical MD and/or PhD, in the references listed. It's granted in the Intro that conventional MDs don't frequently use anything *labelled* OM (convienently overlooking such mega- treatments used w/o recognition...as discussed in Talk before). If you read more of the general Bibliographic material that covers the old medical literature, this stmt is covered and contained in bits and pieces; it is summarized in this stmt. Most of us today will not see such an overabundance of MD/PhD servicing the public as "typical" (figure all MD+PhD is ca 4% at the end of residency). In the context & time of the first introduction/discovery of many OM treatments, the next "treatment" was non-medical & formaldehyde/phenol based... Not bad for ambulatory in a few hours to days in important cases, e.g. IV vitamin C.--TheNautilus 07:32, 23 September 2006 (UTC)

Also will you read *please* the previous Talk sections, it gets repetitious to bring each conventional med proponent even a little way up the information curve on this subject.--TheNautilus 07:32, 23 September 2006 (UTC)

Btw, the specific recognition of the advanced scientific b/g of the orthomed pioneers is not directly an appeal to authority but rather an establishment of their creditials in an often hotly controversial area. Their credentials are especially impressive for their times, i.e. double docs, multiple degrees, years/decades of sponsored conventional research when a high school diploma had about the same standing as a BA today and many MDs only had the 2 or 3 yr version. A number of those unfamiliar with the detailed, underlying science or history of OM have deprecated and lightweighted the orthomed statements and personages w/o consideration that the pioneers were not merely some vodoo queens, wild-eyed charismatic psychos or snake oil salesmen. This seems to be too common an insinuation, even here in these enlightened pages. So, if I err on my verbiage about this, I ask your careful, considered help.--66.58.130.56 07:35, 24 September 2006 (UTC)

A few things...

... first of all, this article is really pretty good considering the controversial nature of its subject and the well-documented difficulties of covering minority/dissident scientific ideas on Wikipedia. Areas where it could use improvement:

• There are a few claims that OM is "frequently used" or that its opponents have been "widely criticized"... but then the citation is from the Journal of Orthomolecular Medicine. It's fine to cite this journal, of course, but it represents a minority view and is not evidence of "frequent" use or "wide" criticism.
• The "strawman" claim runs a risk of abuse. It seems any large trial with negative results is disparaged as being a strawman, not using the right drug, racemer, dose, etc etc... while no comparably robust positive trials can be produced by OM proponents. In science, the burden of proof is typically on the claimant; in other words, it's not enough to disparage every negative study for its shortcomings. OM won't be taken seriously until there are robust, peer-reviewed positive trials. That's not bias or closed-mindedness on the part of "mainstream medicine" (as this article repeatedly implies); it's adherence to the scientific method.
• Negative results are buried. The paragraph under "Criticism" detailing all of the negative/harmful trial results with Vitamins E and A is so lengthy, convoluted, and abstruse as to be unreadable. That's why I had tried to summarize it, although I recognize this is a touchy issue that has been discussed at length before I arrived.
• Similarly, the "Criticism" section is more an impassioned defense of OM rather than a true summary of criticisms by "mainstream medicine". MastCell 19:05, 23 September 2006 (UTC)

A "controversy" approach seems more appropriate when some "conventional" editors insist on airingbroadsiding obsolete, erroneous and highly prejudiced references & arguments since some still think these statements are unimpeachably "mainstream", "correct", or even relevant to *long known* OM forms & protocols. A century of bias, increasingly noted even by mainstream authors, pervades the discussion, testing or interpretation of nutrition, as above Archives of Internal Medicine: 'Tudes & the Anti-Quackery Quacks.. Most of the criticisms and "condemning" tests *do not* pertain to actual OM forms or protocols, hence the oft bayoneted strawman - although I may describe the differences of some cases, this point is obviously still not getting across.--TheNautilus 11:08, 24 September 2006 (UTC)

I guess this illustrates one of my concerns: mainstream, peer-reviewed, reliable-source references are pooh-poohed as "obsolete, erroneous, and highly prejudiced", leaving the Journal of Orthomolecular Medicine as the only "acceptable" source on OM. MastCell 20:20, 24 September 2006 (UTC)

One of my concerns is when mainstreams references that support OM are removed on the spurious grounds that if an OM hypothesis is supported by a mainstream source then it can't be OM anymore. --Michael C. Price ^talk 20:25, 24 September 2006 (UTC)

The presumption of an absolute reliable source because of letterhead or brand in hot zones like this is an especially unreliable practice. I don't reflexively accept or pooh-pooh a paper because of it's JAMA or JOM, I compare the papers' claims with other sources. It's called fact checking. If I use other, more primary sources to show a presumed WP:RS reference is full of errors & misrepresentations such as the pivotal quote source of black balls like BCCA bias & errors, it is not WP:RS as a source of facts, period. At most, it is a WP:RS source of opinion that reflects the nonfactual, bigoted opinions of its notable supporters. Please just don't call it Science, it hurts our ears.--TheNautilus 21:03, 24 September 2006 (UTC)

I'm not suggesting that you uncritically accept everything printed in JAMA, or Annals of Internal Medicine, or wherever just by virtue of its letterhead. At the same time, I think it's important to recognize that articles appearing in prominent peer-reviewed medical journals have undergone a much more stringent process of editing, fact-checking, review, and post-publication critical evaluation than pages on a personal or organizational website (whether it's Quackwatch or the SSE page), or dare I say in JOM. You can assess the evidence critically and reach your own conclusions - that's your prerogative. It doesn't mean mainstream medical journals or organizations are "right" and JOM is "wrong", but it does have implications for how these sources should be treated in a purportedly objective encyclopedia article. After the negative meta-analysis on Vitamin E, the onus is on OM to demonstrate, in an equally robust study, that Vitamin E in whatever formulation or dosage is beneficial. Until that happens, mainstream medicine won't accept it - you can call it bias (and you do), and I can call it the scientific method. MastCell 20:18, 25 September 2006 (UTC)

It was hardly a clean metanalysis, since the authors did not only include pure E vs placebo studies. They also chose to include studies in which both beta-carotene and E had been given to smokers and which showed a very positive mortality effect-- one which could as reasonably been attibuted to the beta-carotene, as the E. And in fact, since the overall mortality effect disappears from the metaanalysis when these studies are omitted, that's certainly evidence that the E is not the problem. However, when this fact was pointed out to the metaanalysis authors in print, they completely ignored it. That's not the scientific method! SBHarris 20:38, 25 September 2006 (UTC)

This is exactly my point. It's fine to poke holes in studies; all studies have flaws, and none is perfect. The meta-analysis is no exception. Mainstream medical practice is based on the best evidence available. Right now, the meta-analysis is part of that "best evidence". Believe me, if a equally or more robust positive study is printed in a peer-reviewed journal, then practice might change. It's too easy to sit back and take potshots, and then complain about bias etc, but that will only get you so far in the scientific world. Let's see an effort to actually address these questions with a better study. That's what I mean when I refer to the scientific method. MastCell 21:33, 25 September 2006 (UTC)

Those big studies are the icing on the cake, to resolve doubts (confirmation) or identify new opporunities (usually surprising results). In other scientific/technical settings, after such a "failure" there might be lots of lower powered investigational studies to develop more semiquantitative estimates and qualitative studies, FIRST. If institutions (ahem) have a poor predictive track record, betting all the money on "36" for only a doubling, spinning the wheel is likely to be disappointing - better to find another game or, at least, another strategy. Metastudies are "best evidence" if they are complete, with no "convenient" selective (in-)exclusions like Miller et al, *and* are truly measuring the same properties, otherwise they are only search or propaganda techniques.--TheNautilus 23:59, 25 September 2006 (UTC)

Also the journals are losing credibility over the *severe* conflicts of interest that keep showing up in the articles with highly biased methods & conclusions that then become official gospel. Medicine's very credibility is draining out with the public despite all the claims & trappings of institutional Science; can't fool all the people all the time. When the workers openly laugh at the mgmt (or the citizens at the elite), the end of the current game is near. Of course, what happens next usually isn't too nice either.--TheNautilus 00:22, 26 September 2006 (UTC)

The influence of $$$ and pharmaceutical firms on medical research is a problem and an area of concern. It's only gonna get worse in the short term with the NIH budget being slashed to pay for Iraq, tax cuts, etc. But when these legitimate concerns are played up by "alternative" practioners to sow doubt, you have to wonder about glass houses. The fact is that regulatory standards for pharmaceutical safety and efficacy are immeasurably stricter than for vitamins, herbs, etc. And it's that way because the vitamin manufacturers and entrepreneurs spent millions in lobbying $$$ to get legislation deregulating their products. There are serious scientists involved with OM/MVT, but there are also any number of unscrupulous snake-oil salesmen who play off the human desire for hope to make a tidy fortune peddling unregulated, untested cocktails. The vitamin/nutraceutical industry is a billion-dollar industry; the money is there to do better studies, but why bother when the $$$ is already rolling in? Mainstream medicine isn't perfect; conflicts of interest exist. But try applying the same lens of skepticism/conspiracism to "alternative" fields as well. MastCell 00:56, 26 September 2006 (UTC)

Conventional health care & medicine is a trillion+ dollar industry with undone OM homework for 2 & 3 generations now, from some of the best, brightest physicians & scientists of their generation. We (the taxpayers) are still waiting. Ooooh, yes, billion+ dollar supplement industry - 1.5c/500mg niacin tab, 1.1c 200mg Se tab, 2c/gm C tab (Costco) - lots of surplus money in OM compared to some poor oncologist with expensive (to buy, not mfr) chemical weapon derivatives to hawk. All Hoffer suggested is maybe $1/day extra supernutritional ingredients added, much less serious stuff like IV C & isoprenoids. Who's gonna pay? We thought we already did, but now what people really demand is the right to simply be left alone, unobstructed & unmolested. That old safety argument is so bogus - drugs *really* do kill & maim in volume, we simply can't trust our govt with any more power. We wish the average doctor knew jack about the high potency supplements (they usually haven't any inkling, much less accurately predict what *really* happens and thereby lose credibility, even on simple, mainstream stuff like niacin). Honest research & testing is ok, but people can't wait any longer and the govt/pharma/medical track record is kind of spotty. I have to admit that cutting NIH funding *might* be even more favorable to pharmas, they already got their money locked in with the Medicare prescription drug subsidy. Soon there won't be any money to pay doctors either. Given only enough money to pay the physician or the pharma, doctors may want to choose sides again, later - if the naturopaths don't lock 'em out first.--66.58.130.56 03:22, 26 September 2006 (UTC)

Preferred vitamin E and controlling for other vitamin levels

This edit [16] raised the issue that authoritative studies with the preferred vitamin E have not been done. However, it then goes on to comment about controlling for "bile, pancreatic function, certain specific heart problems and risk factors, blood levels and cofactors (vitamins C, D3, K1, K2, selenium, co-enzyme Q10, etc.) in the common orthomolecular range, 600-3200 IU alpha tocopherol plus 25%-50% by weight of other R,R,R tocopherols." Controlling for these vitamin levels seems excessive and not routinely done in clinical trials. Furthermore, it's not clear if controlling for these levels actually has a medical basis. (Of course you need to control for heart disease and other comorbidities). Andrew73 12:33, 7 September 2006 (UTC)

Sorry Andrew, I'll have to get back later on this discussion.--TheNautilus 16:52, 8 September 2006 (UTC)

In orthomolecular discussions the direction seems to be broad oil soluble supplementation with specific excursions of vitamins for specific indications. i.e. high dose vitamin E works with some supplementation of the other oil solubles (D₃, K₂, coQ₁₀), some others as redox factors (Se, vitamin C), for specific indications (CRP, angina, claudification etc). Vitamin A is a touchy subject, orthomeds tend toward mixed caretenoids and sometimes with cod liver oil (vitamin A mixture of esters etc & D3, DHA, EPA). Other factors for, more mechanical reasons, such as vitamin C for blood vessel elasticity and thickness (integrity), vitamin K (presumably K₂/MK₄ preferred) for a better, perhaps broader, regulatation between uncontrolled bleeding during injury and unplugged flow where you *start* to use hep or coumadin. In Annals of NY Science ~2004, Jialal mentioned he was interested in the interaction between K₁ and E (orthomeds would more interested in K₂+mixed or high gamma tocopherols). Given Jialal's rate of progress through d,l-alpha-, d-alpha-, binaries might be a while. This graph at Lipids online might suggest why some orthomeds are interested in niacin + mixed tocopherols (or high gamma)high CRP+TC/HDL

I suspect that the orthomeds would use vitamin K₂ to reduce IL-6 (as well as improving osteoblasts for osteoporosis and increasing apoptosis in cancner trtmt), and carbs reduction, Cr-picolinate + Mg-citrate/malate for insulin sensivitivity to reduce insulin. Indeed, when I look at statin research results, the pharmas must be racing desperately to find a superior CRP/IL6 reducing drug to beat d-alpha-tocopherol (not the -yl acetate in ill people, I think that natural medicine types look for or impute gut problems long before conventional medicine does) although orthomeds typically are much more interested in d-gamma-tocopherol for inflamatory conditions (I think it must be through empirical testing in the 1950s). Being a little realistic, I don't expect too much progress testing until someone patents a natural answer included with a synthetic drug vehicle. Do you have any ideas on the MD-PhD funding split between, say straight natural molecules researched (e.g. cholecalciferol research) and pharmaceutical (potentially patentable) molecules ie 5% vs 95% in any of your med schools?--TheNautilus 09:47, 12 October 2006 (UTC)

Andrew73's point is well-taken. The only truly robust way to control for a wide range of variables of unknown significance (eg. "bile, pancreatic function, certain specific heart problems and risk factors, blood levels and cofactors, vitamins C, D3, K1, K2, selenium, co-enzyme Q10, 600-3200 IU alpha tocopherol etc etc etc") is through randomization to ensure that all such variables are equally distributed in intervention and control groups. That's why "conventional medicine" places such weight on the randomized trials that you've expressed disdain for. It's a little ironic that your edits slam RCT's at one point, then slam other analyses for failing to control for all these variables. About the "natural" vs. "pharmaceutical" molecules, I don't know that such a Manichean distinction makes sense, although I see you're once again driving at the corrupting, suppressive effect of pharma. After all, one of the major sponsors of the Linus Pauling Institute is Hoffman-Laroche, makers of much of the world's Vitamin C. MastCell 21:22, 12 October 2006 (UTC)

There's too many misconcepts here to fully address tonight. A better stmt would be that truly robust science attempts to control multiple variables by measuring and manipulating them all, singly and in combinations, and measuring the results. Conventional medicine (pharma & entrenched specialities) seems to have a special knack for avoiding this where favorable results would be financially unfavorable (ie cheap, effective, nonpatentable, or at least noncontrollable, answers). Randomization is an attempt to overcome unknown & uncontrollable variables by brute force. It makes little scientific sense to keep sticking one's head in the sand by refusing to at least measure, if not control, the known, or suspected, variables. One good test beats dozens or hundreds of crumby ones. Improved measurement, not (massive) randomization usually drives new scientific results. Also one has to be very careful in multivariate problems to get a full mapping, in concentration range, time and combinations of vasriables- an area that conventional medicine persists with slow, single variable approaches & poor measurement techniques that are guaranteed to utterly fail. Conventional RCTs frequently misrepresent orthomed time-concentration products by a factor of 100 or more, with "wrong molecules" as a frequent favorite ploy, as well as poor measurement & controls. "Modern medical research" reminds me of going to Russia in the 90's, seeing incredibly obsolete things that my grandfather had better understood, having recently passed away at the tender age of 100. I slam the RCTs of medieval, er, modern medicine because they are so s---ly designed and executed that in many cases I don't infer incompetence, even granting the brainwashing exercises in pat but poor answers that one gets in med school (which I have observed), herd mentality survival skills, and lack of heavy, independent technical b/g for most. Natural moleculaes, you know - the unpatentable ones, that occur ready made vs the often inferior, patentable ones, "pharmaceutical grade". (e.g. Snodgrass' negative quotes about vitamins, in the illiterate skeptics' much adoredBC Cncr Agncy attack page, he complains about the inferior "industrial" - twisted, altered, doppelganger - versions of vitamins and clearly wants the real thing). I am going to need more time and space to explain how perturbing a single variable slightly in multivariate terrain, is totally inadequate to handle large, logarithmic ranges with obligate codependent factors - almost guaranteed failure. My basic complaint is that huge amounts of money have been wasted on ineptly & prejudically controlled testing that have ridiculously weak scientific foundations for multivariate problem solving, given the known, preliminary & suspected variables and answers.--TheNautilus 11:05, 13 October 2006 (UTC)

Hmmm... I think most biostatisticians would feel that attempting to control for numerous factors of known and unknown importance through multivariate analysis is in fact the "brute force" method, whereas true randomization is a much more elegant and robust way to ensure that such factors are evenly distributed between the test groups. Your statement that "robust science attempts to control multiple variables by measuring and manipulating them all" is misleading; a more accurate generalization would be that robust science attempts to alter one variable at a time, while keeping others constant, so that the effect can be precisely measured. That, rather than greed or incompetence, is why RCT's are so highly esteemed. You don't have to agree, but be aware that you're placing yourself at odds with fundamental precepts of science; that, combined with your tone of overarching contempt, may explain why your point is failing to get across. MastCell 18:26, 13 October 2006 (UTC)

I start to compare Single variable testing to infinity, 101 vs Real time Multivariate testing 601 in test design links below, along with some peer reviewed article results also noted. Its long way to Tipperary.--TheNautilus 10:25, 14 October 2006 (UTC)

B-carotene & "vitamin E"

Not exactly first line orthomed molecules, mixed natural caretenoids incl'g recent lutein & lycopene would be more interesting. Ditto the much belabored toco- cmpds. "Strawman" issues right up front; cherry picked subpopulation for *known* problems such as the smokers and synthetic beta carrotene is covering a POV in glory - a common form of beating the strawman. Miller's little meta-analysis had so many problems they're hard to comprehensively list. I'll have to work on Topol.

"Nonetheless, several large and well-conducted analyses have shown that high-dose Vitamin E supplementation does not improve^[1] and may even worsen health.^[2] High-dose beta-carotene (Vitamin A) has been shown to increase the risk of lung cancer in heavy smokers.^[3][4]"--09:32, 23 September 2006 (UTC)

Er... I'm not sure how the quoted statement represents POV. It describes the results of several large trials in the terms used by their authors. Textbook NPOV. If you prefer to remove "well-conducted", that would be reasonable. I know you personally feel that the "little meta-analysis" had "too many problems to list", but asserting your interpretation of the validity of results is, in fact, the POV violation here - not to mention OR. Finally, I know you like the strawman argument, but you're being paranoid. Carotene proponents claimed it could prevent cancer; smokers are at high risk for cancer; ergo they represent a logical population in which to test the intervention. This is Statistics and Clinical Trial Design 101; imputing a sinister motive ("cherry-picking"?) in studying smokers is ridiculous. MastCell 21:06, 12 October 2006 (UTC)

"our..., the POV violation here - not to mention OR" my comments on meta-analysis are considered trivially true in technical circles, you should satisfy yourself about this. The complaints about Miller et al even in pharma financed carriers are legion, if muted. Of course, Miller gets the last word...

I am not paranoid, here's one NEJM editor generally agreeing, another and similar, sandbagged RCT criticism, more on RCTs. Repeating a known "bad" result for a narrow case, again and again, portraying it as a major, new broad result is a form of strawman attack. The beta carotene results for heavy smokers were conclusive the first time - bad news for smokers. The carotene results are favorable for non smokers, beta-carotene, the synthetic, as been considered suspicious for 20+ yrs in natural nutrition circles (my limits of recall). Annoying the 3rd time on the same molecule (b-c), where this result is then used disparage another important molecule(s) that aren't even used (tocopherols not a- -yl esters) as well as potentially misleads others on carotenes (nonsmokers? all 600 carotenoids? even in long used natural sources e.g. colored veggies & carrots by the pound).--TheNautilus 11:31, 13 October 2006 (UTC)

Here's why I bring up paranoia: we're talking about why smokers were studied; I suggested it was because they were a high-risk population for the outcome of interest; and you cite a bunch of books about the evils of big pharma. You seem to be ignoring my point while alleging a conspiracy to "disparage" beta-carotene; I'm not clear on who the benficiaries are, since there are no competing patented drugs for the indication in question. I know you believe your comments are "trivially true" (??), but they represent your POV and OR until they are adequately sourced. This is Wikipedia; the onus is on you to add sourced information, not on me to "satisfy myself" that there's a wealth of support out there for your POV/OR. Finally, I'll repeat that the phrase above in question is textbook NPOV and presents the conclusions of major, peer-reviewed studies in their own words. You can add sourced criticism of the studies; you can't unilaterally disparage them on Wikipedia based on your personal views. MastCell 18:37, 13 October 2006 (UTC)

1. "we're talking about why smokers were studied" no, in the OM article we're talking about "vitamin E" & tocopherols, using a narrow, special subclass (smokers), apparently adversely controlled by b-carotene factors, to condemn potential tocopherol treatments that are neither controlled for known cofactors or meet long used OM tocopherol minimum threshold amounts, or a factorial design. (note isoprenoids often are more powerful antioxidants than tocopherols, potentially interfering with tocopherol metabolism, by reacting first, and yielding different metabolites.)
2. "since there are no competing patented drugs for the indication in question" "no competing..." sounds like uncertain OR, esp'lly presuming what's patented (or applied for) lots of things, possibly still in the pipeline.
3. not to""disparage" beta-carotene" No, sir. To disparage tocopherols and perhaps other carotenoids/isoprenoids that may be competitive. Isoprenoids (20,000+) have lots of pharma patent activity recently in force.
4. I do not dispute testing subcategories (e.g. smokers), I protest vast, loud overgeneralization and misrepresentation of negative results to certain, specific chemical combinations & patient subclasses, especially in reruns w/o significant new information content.
5. I do not think that I am required to teach basic calculus when I refer to it; ditto statistics & test design. I agree, the experimental methods used in medicine today are Statistics and Clinical Trial Design 101, that's the problem. More advanced articles for Operations research, Response surface methodology, Design_of_experiments, Factorial_experiment, A Role for “One-Factor-at-a-Time” Experimentation In Parameter Design gives some design insight but is by no means exhaustive. Factorial, multivariate experimental design in real time 601
6. "sandbagging the test" charges are often non-mainstream Factoids, and, also, Ten Ways to Spot Anti-Vitamin Biases in a Scientific Study, but easy to verify by inspection. The last two books, above, do discuss rigged & misreported RCT problems in the mainstream, too. Here's a letter about a rigged test from a 1994 JAMA article, criticized by Joseph Keenan et al, MD, niacin researcher at UMinn: "The study by Dr McKenney and [Merck] colleagues is described as a well designed clinical trial.' We would concur with that description if the authors would make more explicit the intention of the study, namely, that it was designed to maximize the potential for niacin intolerance and toxicity. Despite their obvious unfamiliarity with the literature, they chose a particularly unphysiological twice-daily dosage schedule. Similarly they escalated the [plain niacin] and [time release niacin]..[to] intentionally administer a dose that exceeds that toxicity threshold by 50%." Hmmmm, sounds like careful, objective, peer review process for articles at JAMA, uninfluenced by all those glossy color statin ads.
7. "can't unilaterally disparage them on Wikipedia based on your personal views" I am seriously trying to explain through this little keyhole in the fog why mainstream tests for dbRCT *are contested & disparaged* in orthomed for time, costs and lack of results.--TheNautilus 10:18, 14 October 2006 (UTC)

Let's go back to the sentence you initially took issue with: ""Nonetheless, several large and well-conducted analyses have shown that high-dose Vitamin E supplementation does not improve^[1] and may even worsen health.^[2] High-dose beta-carotene (Vitamin A) has been shown to increase the risk of lung cancer in heavy smokers." Let's leave out the "well-conducted" - do you dispute any other part of that sentence? Also, you're citing literature from engineering. Clinical trial design/biostatistics have important differences compared to physical sciences like engineering or physics. And it's not because everyone in biostats/medicine is stupider than you and/or corrupt, as you imply. Finally, accusations of "OR" make absolutely no sense on the talk page; everything here is "OR". MastCell 17:03, 14 October 2006 (UTC)

The "vit E+ b-c" sentence is misleading because a conventionally informed reader, even or especially doctors, will presume that the result represents a test of relevant orthomolecular regimens, which it does not. Not even close. As for test designs, engineering and related bio- fields have used factorial methods outside the laboratory for decades now. The "medicine is really, really different" theme, perhaps "too much for the unwashed to understand" variously sounds alternative universe, and like the socially caste, preliterate, 18th century in its appeal. Medicine is simply somewhat behind in applying modern test design methods to field scale trials here (my surmise, absolute necessity is often the driving force in other fields, and that we haven't faced the ultimate financial health crisis that *might* connect institutional survival to serious, success oriented, nutrient research). Re more stupid or corrupt, not exactly. Blinded, hobbled, preprogrammed, swept up, struggling to survive in a broken system, (pre)college to retirement, most people can try to struggle honorably as they can w/o overall direction, recognition, or effect in a maze with respect to the orthomed paradigm. I would say that there are pervasive, pronounced, systemic sources of distortion of which many of those "inside" seem either blind, resigned or inured to. Even the mainstream observers have commented on evolving anti-nutritional biases in major medical textbooks (Cecil's, Harrisons) over multiple editions[17].--TheNautilus 21:44, 17 October 2006 (UTC)

You're incorrect. A "conventionally informed" reader or doctor will read the sentence (which is 100% factual and NPOV) and presume that Vitamin E and beta-carotene have been tested. Which they were. If interested, they can click on the reference and examine the paper themselves. That's how Wikipedia works. It's really not your place to "protect" the reader by spinning the study. About test design, head over to the local library and check out a few books on biostatistics or clinical trial design. You'll see that randomized controlled trials are the preferred method for establishing causality in medicine and evaluating treatment interventions. Either a) you're smarter than the textbooks, or b) you're wrong. It's ironic that you accuse your opponents of arrogance and elitism, and then constantly express sarcastic frustration that those who disagree with you are hobbled, brainwashed mercenaries who are incapable of understanding your lofty arguments. It's also ironic that you disparage the ethics and intelligence of conventional physicians, and then carefully gerrymander "orthomolecular medicine" to exclude the snake-oil vitamin salesmen and other nefarious specimens who are associated with it. MastCell 03:37, 18 October 2006 (UTC)

Unfortunately, your answer is a total miss here. I think my answers need to be reread in the light of a much criticized medical system or industrial complex, that is in fact greatly burdening doctors as individuals, rather than directly accusatory of the individual doctors (look at my edits, I am actually aiming at pharma related stuff). If my words seem too harsh to you, I do apologize - I am sure you have studied & worked hard for what you know, what you think (you appear to be a MD-PhD as well as specialist). A much critcized aspect of conventional medicine in the popular literature, is that in the hurly-burly of medicine those conditions that it doesn't understand or identify well are often denied, even unto death. Other systems, in the experience of their patients, seem to address these areas sooner, perhaps even better. One probably could account for a number of orthomed successes in this group (review the patients' books on many missed diagnoses that involve decades, if ever) as unrecognized but complex malabsorption, given the naturopaths' literature emphasizing digestive & gut issues upfront. (I actually think the debate about / between SIBO-leaky gut-"Yeast" is going to resolve in the not-so-distant future.)

On your note:(1) Again, my complaint is that the particular vitamin E and b-carotene trial was of little orthomed relevance, being disproportionately played as if it were part of a "vitamin E refutation" following Miller - wrong molecules (mono-carotenoid, -yl esters, and some were big on gamma-tocopherol content for 2/3 of century - a "better" representative formula, Unique E, marketed ~1962, is not a sudden bait & switch item on composition here), wrong doses (1000-3200 IU alpha + 25-50% gamma, up to 200% beta, gamma, delta tocopherols w/w ??), uncontrolled for those diagnoses & chemical factors documented in the literature as important but apparently still on the future "exploration & discovery" list for some. e.g. see Jialal thinking about testing vitamin K interactions with R,R,R-alpha- or gamma- generally in the NY Annals as well as other researchers. Hopefully selenium, vitamin C, coQ10 as cofactors for tocopherols aren't too controversial in conventional medicine now. The vitamin C & K parts are considered important variables, in part by some, to slow, prevent, stop or reverse blood vessel wall thinning and bleeds (that plague conventional thinners more), part of the many reasons one hears about "balance". I'm not "protecting the reader", I'm editing an article often completely misunderstood &/or misrepresented by its critics, frequently based on hearsay.(2) About test design, the (multi)factorial design part is independent of whether or not the test is (or is not) a RCT, your misunderstanding, not mine. And I do understand that RCTs try to cancel out errors by randomization, but better measurement & control are still a "bigger, better, faster telescope". (3) Take a good hard look at this OM article, its talk page, see if my sarcasm hasn't some basis (although I may need to work more on defensive attitude now). I must admit that several previous (too lengthy, still incomplete) attempts at my last note were more buffered concerning this since we have been able to rationally come to terms on articles. (4) When I criticize "medicine", I criticize the "system" doctors learn, live & work within, - although I do believe most doctors to be well intended. (5) true orthomeds want no part of "snake-oil salesmen" but they are often past the waiting-for-Godot on botched conventional testing (most aren't even subtle, i.e. 1 vs 100x on dose-time product, wrong molecules) although they would love to see more incisive, useful work, they have literally been waiting for generations.

Your words reinforce the idea that many conventional doctors have a lot of suspicion about orthomolecular medicine, and again, simply lack a lot of real familiarity on its (pre)history, protocols and rationale. Sorry, that's why the books & links are referenced in the article, but it will take a while to read & digest.--TheNautilus 06:17, 18 October 2006 (UTC)

First off, your point about tone is well-taken. I could stand to be less defensive as well. I do think the arguments about mainstream medicine's hostility/closed-mindedness toward OM are a little overdone. I'm not picky; I'd happily treat people with vitamins, magnets, imagery therapy, crystals, or whatever in place of statins if they were shown to be more effective. I think this is true of a majority of "conventional" physicians. I've referred plenty of folks to chiropractors for back pain, as this is supported by the evidence. The problem comes in when the claims overreach the evidence; in other words, I wouldn't send someone to a chiropractor for heart disease. The fact that pharmacuetical firms sometimes behave unethically doesn't make OM as effective as statins. I think "true" physicians would happily dissociate themselves from the excesses of pharma or the AMA (as you'd dissociate OM from snake-oil salesmen), but don't have that luxury. I'd be the last person to argue that the current medical system is perfect; it has more than its share of flaws. But as Churchill said about democracy, it's the worst system except for all the others that have been tried. OM proponents can keep passively waiting, or they can get involved and actually produce meaningful research that will change practice patterns. Lots of folks at mainstream, large research universities are working on these issues (witness the firestorm of mail in response to Miller's meta-analysis); the money is out there. When there's some robust evidence, practice patterns will change, as they did with niacin for dyslipidemia. MastCell 19:52, 18 October 2006 (UTC)

Glad you mentioned niacin & statins, it's a fairly good area to look and understand some of the problems of orthomed. I'll come back to it.

Orthomeds are not passive - they are in exile, doing what they (generally speaking) can with what little they have. If you see some rich, nominal orthomed, it may mean they may have commercial ability gifts; case dependent. The big money largely flows along company lines. The really hardcore orthomed research is largely historical, those MD-PhDs of yore that still could get pharma funding back then (1950s & before, pre-orthomolecular exit strategy from natural to patentable molecular medicine). Other than that, a few individuals, here and there, working themselves silly, if not to death (Horrobin?). In my eyes, today's mainstream MD-PhD that skirts too close to the orthomed flame, burns - don't dare say it's orthomed... or else, one's support dries up like a fig leaf in the Sahara. A lot (most?) of the "alt med" govt funding appears to go into funky & palliative treatments that constitute little threat to pharma interests, that funding which pertains to orthomed seems to explore (often strange, deficient or lower) dose regimes that orthomeds would actually be pleasantly surprised to see work but don't much hold their breath.

It is presently *extremely* difficult to directly develop an orthomed cognizant physician-scientist in today's med ed environment, realizing a "plain" MD-PhD is increasingly hard to sell to the students. Take a biomedical group of 20-30 students doing summer research pgms. Ask them what they really want (PhD, MD, MD-PhD). Most are really going for the MD and the country club, the nominal PhD one(s) is actually the MD-PhD hopeful(s) (I can't cite my OR, but the Shadow knows...). Everything the kid has in college will go into getting into a hoped for "better" medical program, & financing it, all the while trying to have some kind of life amidst a very uncertain application system (at the end of 14-24 grueling months, some are in with *one*, some are in at many but will not get the real plum until May or June, and, of course, many are just SOL - who's going to rock the boat?). Are the successful MD school candidates going to lead with their chin getting in? In the US, they probably better keep it mum, and expect to wear sack cloth and ashes afterwards if they are orthomed interested at all. From what I see, genuine orthomed research has become the province of energetic (near) retirees still willing to do research, with their own $ & lab.

On the statins, the orthomed story is of interest. Niacin, I believe, is still the only "cholesterol" treatment with clear improvement to 10+ year all-cause mortality, even on lower doses, e.g. the non-continuous (average 6 yr treatment) CDP trial. The statins, despite the run in (run off) period eliminations of the coQ10 & myo- "weaklings", seem to lose long term steam on all cause mortality over the years. (On poorly controlled, "pharma-phriendly" niacin trials, the early dropouts may be among the ones that could benefit the most - you flush, you stay, you win - where good niacin doctors only lose 3-5% on compliance, pharma niacin trials will drop 30-40% early on - hmmm) Watching the journals I see disparaging niacin articles that are clearly pharmaceutical POV but I guess younger readers take them seriously since they did make the journals. The good niacin results reported lately are mostly ones that improve a statin result. One of course realizes that the CVD biomarkers and risk factor weightings remain up for grabs. Niacin is still largely an orphan treatment in CVD (try to name a doctor under 60), despite its demonstrated ability to remarkably clean up many profiles and sometimes promptly resolve angina in minutes. A number of the older doctors that are intimately familiar with the previous niacin research & clinical experience, still think that niacin is superior in the majority of cases, and that the most recent statin, er cholesterol, guidelines suffered greatly from ahem, structural economic problems. Similarly high dose (think 600-x000 mg/d), high gamma content, mixed tocopherol mixtures on nasty angina cases in a fews days/weeks, with happy individuals for decades. Is that vit E with or w/o vit C? On beta carotene that there may be collision between therapeutic molecules and conditions is of interest. Even NEJM apparently was concerned that the beta-carotene trials' negative reflected an unreduced (unrecycled) hepatotoxic metabolite of b-c because of the extra, unfilled oxidative stress of smokers (where's the extra 25+mg/cigarette of C calculated ~1950s?) Hence the interest in factorial trials, even small, low powered ones rather than rare, serialized big ones which would benefit from small *public* multifactorial trials, first - indicative terrain mapping exercises.

Although I do see increased number of small trials in nutrients more recently, it's hard to class them as orthomed because their compositional/frquency schedule starting points are so different, where orthomed already pretty categorically states that some megadose molecules *are* coupled, and some are more frequent - vit C 4x/day & at least some B's. How about starting from some "healthly person" OM vitamin recommendations (OMDA?) on the broad vitamin front, A-K (or Q) ie, say 8* 1989 RDA on water solubles (B's & C) as well as enhanced minerals and oil solubles (A,D,E,K) with the "right stuff", *then* preturbing 1 or 2 components (much) higher and/or controlling against the RDA amounts with standard form (cheapest) vitamers (warning: this means ~4x / day preferred for water solubles).--TheNautilus 05:11, 21 October 2006 (UTC)

I think you're being overly negative about the use of niacin. When I was in general medicine (not that long ago), I frequently prescribed high-dose niacin/nicotinic acid for folks with low HDL. It's the most effective pharmacologic way to raise HDL (of course, exercise, wt loss, smoking cessation are even more effective usually). Of course, it's often combined with a statin since statins are effective at LDL-lowering and have mortality data as well. But unless things have changed drastically in the last few years, I would posit that niacin is widely used by "conventional" practitioners for the treatment of high-risk pts with low HDL cholesterol. MastCell 15:52, 21 October 2006 (UTC)

I would say that your niacin usage is far better than my average inquiry with doctors (n=20+), and since "intermediate dose" niacin is being revisited by some pharmas for HDL, perhaps a growing trend. To me, "high" means 1.5+ g sustained release, and 3+ gm pure niacin, up to the therapeutic limits. Niacin as primary for mixed dyslipidemias or *any* statin problem (e.g. a friend was trialed on statins 5x with disconcerting side effects until rectal bleeding occurred, and the mention finally was "well, have *you* tried niacin"...no real support; another ran low on coQ₁₀) seems to remain obscure and not well supported in many instances. Optimum niacin results take knowledgeable perhaps careful support i.e. can anyone you know knock LDL down 50+%, or as desired & raise HDL 50% in *some* solo niacin cases? (looking at those statin studies, personally I would still focus on HDL, Lp(a), homocysteine, CRP, Mg, K, iron in 1/10 males, insulin/BG/HAc, naturally of course ;-). The detailed niacin story has often been a good first guage of how orthomed aware a conventional doctor is (and the answer has been, pretty much, 0).

Seriously, back on the beta-carotene/"E", trials there are several things that are like a stick in the eye to an orthomed. There are least two things that automatically stick out as non-orthomed: (1) although you will seldom see a hard recommendation for a vitamin C schedule & dose (remember, individualization) basically full, principled orthomed, *for a healthy body*, starts at 4x/day (closer to constant blood levels based on pharmokinetics, roughly known since the early 1940s) and 4-5 g/day. Anything under, say 0.5g x 4 or 1g x 3, simply doesn't sound very OM any time, any place, although an OM would probably encourage anything above RDA and 2-3x/day. Not checking vitamin C residuals, tsk, tsk, since even NEJM mentioned vitamin C residual as required for an antioxidant reserve for carotenes (that hepatotoxic oxidized metabolite), well too bad expendable Finnish smokers don't read NEJM too carefully. Guess they'll have to do it again. (2) Although an orthomed probably will favor any "E" over none, anytime one sees less than 20% beta, gamma, delta tocopherols, there is a high index of suspicion about orthomed content. The d-alpha-tocopheryl succinate tissue redistribution and pharmokinetics are interesting because of some people's "cell proliferation problems" and the need for a stable, dry multivitamin (how about gamma- succinate too, folks?). Because of oil solubles transport issues, an orthomed looks (ahem) for indications of adequate bile & enzymes. CF is not the only situation where pancreatic enzymes fall short for oil soluble vitamin transport requirements. Routine or even simple bile & PE checks are an "underserved market" in conventional medicine. These kind of trials like the smokers b-c+"E" of course help build a factorial data matrix, they simply aren't orthomed unless they add *some* positive evidence of efficacy to the current paradigm and protocols. Frankly the (conventional) test protocols that fail to consider (or document) these variables look pretty weak (absent=0.000) by orthomed precepts, hence my comment to Andrew about control or measurement of at least *some* data on C, E, K, Se, PE, etc. The obsessive, absolute high statistical power requirements of 2-3 std dev. or it's voodoo, without strong address of known variables, as well as the magnitiude of net benefit (such high precision becomes important as net benefit approaches 0+ or even a little negative, 0-), reminds me of kids in school fastiduously using calculators to track all 9 digits of an incorrect answer, of say 1/99, when the correct answer was pi, laughing at the kids who only wrote 3.14.

The "smoked" b-c+"E" trial certainly says be careful about taking random, large supplements willy nilly (tests ignored prior literature and practices, at least relevant to an orthomed), and, perhaps, trust but verify - monitor (HMO?) population statistics and consider tests on an ongoing basis. *That says nothing about orthomed* - how would you feel if some adult complained about "bad conventional medicine" because they got ahold of a bottle of Seconal or even Tylenol, and started gulping? Darwin awardee?--TheNautilus 05:35, 22 October 2006 (UTC)

I guess I'd feel like those drugs (paracetamol, Seconal) were heavily tested prior to their approval, and optimum doses and toxicities defined. If someone ignored those optimal doses, I wouldn't take it personally as a reflection on conventional medicine. The difference, to me, is that megavitamins are being advocated for use in ways that haven't been fully tested, nor have optimal doses necessarily been empirically defined (although obviously many opinions exist). About study power, I know we differ in our takes on clinical biostatistics, but p-values and statistical significance exist for a reason. You're asking for orthomed treatments to be held to a lesser standard of proof than the pharmaceuticals you scorn, and that's why many "conventionally trained" physicians are skeptical. MastCell 17:04, 22 October 2006 (UTC)

"If someone ignored those optimal doses, I wouldn't take it personally as a reflection on conventional medicine." Similarly, if someone ignored those empirical protocols with multiple sources, we wouldn't take it as a reflection on orthomed, either. The very pooint of discussion.

"nor have optimal doses necessarily been empirically defined..." you probably aren't aware of a lot of pre-1965 vitamin research, seems the orthomeds and naturopaths are among the ones who have scoured it most, "modern medicine" seems content to ignore or even disparage previous generations' research w/o adequate review and outrigh deletionism in the texts (something very impressive & useful disappeared between 12^th and 16^th ed Harrison's), as well as current advocates who are pretty heavy duty on science. Often the conventional perspective is highly distorted by negative findings that, well, weren't properly tested, followed up, analyzed or represented on crucial tests. I'll lead off on Sabin (1939) and Moertel (1986) for IV/IM vitamin C where most people can only access (observe) Cathcart's oral protocols, there are multiple independent observations of dramatic results by qualified personnel, evidence akin to confirmation in the physical sciences by independent observers.

By orthomed and US legal standards, vitamins (& vitamin-like substances) are food rather than drugs, explicitly recognizing the different risk-benefit profiles. Also one could fundamental disagree as to the degree of additional testing on natural products of human necessity in terms of prior empirical testing, both by evolution and consumers. A new drug starts out as one of millions of frequently toxic chemicals in the laboratory that is appealing for parole and has little or no previous human exposure. Drugs have been mostly evaluated for immediate, short term, specific effects with rather poor but somewhat improved long term monitoring, which has already shown the "poor" part. Orthomeds have been critical of many "proven" drugs because of their long term sequelae & rather dim (or unproven) all-cause mortality. (One of the reasons Pauling got in trouble with Medicine in the 60s-70s was that in his goals, criticism & testing, then unusual, he stressed all-cause mortality as the principal test criterion - ugh!).

New medical trmts might map to a long term, all-cause net benefit range, say (-0.1 to 0.33), ignoring the occasional fugitives, -1 (based on some horrid examples we've seen in the papers with safety trials). Orthomed, based on experience, is mapping (0.1 to 0.4), accepting occasional -0.1 fugitives and crying foul over some censored +1's. Crossing 0, and remaining near 0.0 more frequently, new drugs may *need* higher resolution tests, say 0.01, to show net benefit (or not) near 0.00 to avoid disposing of "salable" new products and yet reasonably avoid public travesty. Orthomed may be comparatively safe successful with 0.1 sensitivty starting with safer products. This is partly why the public is starting to become skeptical of conventional medicine, especially under the ubiquitous pharmaceutical presence. "p-values and statistical significance exist for a reason" but are somewhat situationally arbitrary, major medicine won't touch this except under the most compelling circumstances, and then the other hand

One other item on the beta carotene-E tests. I have shown some of the orthomed thinking in this area. Earlier, I said not even close on composition. The closest natural product formulas were the "ACES" formulas of 25+ years ago, typically about 6 - 15 mg b-carotene, 500 mg vit C, 400 IU alpha-tocopherol (then often, all rac- -yl acetate), about 50-100 mcg Se, in one or two caps. At 30 mg b-c, these tests would short antioxidants 800 IU alpha-tocopherol (400-750 IU tocopheryl moiety), 1-2.5 grams of vitamin C, and substantial Se. Orthomed then would add more C, gamma-tocopherol (in practice, beta-, delta- too), and, now, a host of enhanced vitamins and minerals. The modern ACES formulas have tended to evolve toward mixed caretenoids with less b-c, natural tocopherols, more Se, more other minerals and antioxidants. The b-c debacle may have given more credence to the previous natural food analyses & epidemiologic studies, and their advocates, to strengthen proponents case for the mixed caretenoids & mixed tocopherols formulas over the "industrial" vitamin sources.

I think that I have shown why conventional medicine's b-c+"E" trials, although somewhat relevant to defining *what is not* orthomed, never fit within orthomed protocols, reasoning or this article well, and at the very least are greatly overplayed for length, negative conclusion and relevance. Using these trials as examples says more about what conventional medicine mistakenly thinks orthomolecular medicine is; this problem area is already covered in the article. Such an example confuses people about what kinds of approach, protocols & products OM really does use, advocate and why, as well as disparage the subject.--TheNautilus 10:30, 23 October 2006 (UTC)

I'm going to take issue with a couple of statements. First, "By orthomed and US legal standards, vitamins (& vitamin-like substances) are food rather than drugs, explicitly recognizing the different risk-benefit profiles." Yeah, and also explicitly recognizing the millions of $$$ that the supplement industry spent on lobbying and PR to push through the Dietary Health and Supplements Act of 1994, ensuring that they would stay unregulated and did not have to meet safety and efficacy criteria from the FDA. It would seem hypocritical to go after big pharma for its influence and corruption, but ignore the weight and money that the vitamin/supplement industry throws around in Warshington. Next, "A new drug starts out as one of millions of frequently toxic chemicals in the laboratory that is appealing for parole and has little or no previous human exposure." Sure, some drugs start life that way. Many, however, start as one molecule in a natural or herbal product, mixed with many toxic natural compounds... and attempts are made to separate the useful molecule from the toxic "natural" ones. Making this kind of distinction about "artifical" pharmaceuticals and good "natural" products is almost always arbitrary, misleading, and meaningless. The measure of a drug is its efficacy and toxicity. When people focus on how "natural" a drug is, it's often because there's no data on its efficacy or safety. MastCell 11:13, 23 October 2006 (UTC)

Nothing is free in this country anymore, including the country & people. Million$ are chump change for a survival issue and rights. The pharmas spread their billions around *everywhere* and everybody, some more physically direct than others. Since a lot of the basic manufacture of many vitamin forms actually come from pharmas, I am left wondering whether we are actually criticizing the same companies in some cases.

The DHSEA 1994 reform was precipitated by the FDA's televised, armed show of force on Dr. JV Wright's Tahoma Clinic in 1992. If some supplement suppliers were able to tap that popular surge of outrage to help some kind of reform, great. Much of the public really has had enough. I mention natural vs artifical with reference to vitamins because in the oil solubles it has made a great difference in relative toxicity and performance. I am not discussing herbals vs pharmaceuticals, you're fast getting into non-OM naturopathy - I'm not an herbalist. I don't really care where molecules come from if they make spec, in many cases natural is still the preferred source. ie (currently *the* synthetic) form all-rac alpha tocopheryl acetate appears to be substantially inferior to mixed RRR-alpha-, beta-, gamma-, delta-tocopherols for many high dosage uses, ditto vitamin K, compare "K₃" vs K₁ vs the research on the menaquinone-4 vitamer of K₂, there's a BIG difference, as with some others. If this "natural mixture" can come bioidentically from some stereospecific osmium-xxx sieve catalyst or some pet, gene-transferred yeast, terrific, then I don't care. When it comes to vitamins & minerals, orthomeds have been very discriminating about some vitamer molecules. Despite our politics intruding again, can you see the point in my discussion about b-c/"E" not really being OM relevant?--TheNautilus 13:01, 23 October 2006 (UTC)

I guess what you see as a "popular surge of outrage", I see as astroturfing and PR. But we can agree to disagree there. Back to the study in question: of course I don't think the meta-analysis or the other study I cited "debunk" OM, nor do I think we should stop studying vitamins. I do think that the studies need to be mentioned in this article, in plain language (as I proposed above). You're welcome to add sourced criticism of the studies to the article as well.

The problem with the studies you propose is a lack of feasibility. A trial without randomization, attempting to control for all of the factors you've mentioned, and manipulating all the variables of interests seems like a logistical nightmare, and I say this having been involved in clinical trial design. If you have a way to do it, by all means let's generate some data. But the reality is, any study of these topics will have methodologic limitations (like Miller's meta-analysis). At some point, the field needs to move beyond criticism of existing studies and be constructive: find a way to do it better. I really harbor no animus toward vitamins; I'd happily use them, but I need proof. I think this reflects the sentiments of many practitioners.

I'll confess I don't spend a lot of time scouring the pre-1965 medical literaure. Because, well, things have changed. I could quote studies from the 1930's and 1940's in support of lobotomy as first-line treatment for schizophrenia, for instance. But the field has advanced (some would say, not far). The fact that OM is citing studies from 50+ years ago is a red flag. These treatments were actively studied, and then abandoned. The logical conclusion is a lack of efficacy. Sure, there could be a conspiracy of suppression at work, but I'd require some evidence to believe that. It doesn't change the fact that most physicians won't use a treatment that hasn't been proven effective in modern medical literature. MastCell 18:18, 23 October 2006 (UTC)

"popular surge of outrage" is when their blood boils on the first news, agitative PR is what happens later, before the revolution (I've actually been there when a real revolution was born, and almost got ran over by armor, whereupon I decided to leave. The popular outrage started with the first day's censored newscast).

I think fair, relevant studies are appropriate. Leaving out critical, known ingredients w/o controlling experiments or data and drawing premature or biased conclusions, gets one in trouble in other disciplines. As for revisiting old data, the trick is to dissect old observations with the eyes of a modern, works best with extensive cumulative even obscure knowledge (unusually well informed in several areas or fields). This is actually how the laser was invented (& hijacked by a professor), kid (Gould) re-examined Einstein's notes from the turn of the century (and after an investigation by the NAS(!!), a belated fundamental patent issued 20+ years later). Productive, scientific producers of *fundamental* patents often utilize this approach.

Miller's meta-analysis shows all the ills of an abused methodology. In days of yore, using meta-analysis w/o tight, well controlled matching of parameters (statistical addition of means and error w/o selection) was a sign of amateurism or even fraud, then it became speculative (well, close enough, assume the parameters happened to match) as a "search technique" to be followed up by better testing. Now it's the darling of medical-political warfare, used to terminate further consideration, see the news at 5 and journals. hmmmm.

"A trial without randomization..." Again, my suggestion does not exclude RCT. It does require insightful (possibly new, multiple) technique, planning & work, harder &/or smarter on the measurement techniques and cost control (will your data include *some* good biomarkers, even if currently unresolved?} Run a low power, but still useful/indictative factorial trial to debug and identify the hidden issues. Been there, done that, in circumstances most quit (& couldn't start).

I have no sympathy for the *powers that be* (where the funding is), not generating adequate data or sharper, new techniques. Deadlocks actually resolved usually come about through superior insight at the analysis & synthesis levels with improved data (not just recording more & again). Systematic refusal or inability to correctly address the issues breaks down sooner or later, such as Moertel's subversion of Pauling, with some of Pauling's pointed criticism validated in the mainstream as of 2006 (Pauling wouldn't even have to be right about vitamin C). Practicing doctors passively waiting to be spoon fed the answer is wearing thin with the public, and yes, I realize there are social / institutional barriers, too.

The fundamental problem with your proposed sentence ""Nonetheless, several large and well-conducted analyses have shown that high-dose Vitamin E supplementation does not improve[1] and may even worsen health.[2] High-dose beta-carotene (Vitamin A) has been shown to increase the risk of lung cancer in heavy smokers." [18] is that the experiment was not even close to reflective of orthomed recommendations of the day, then. The test concerns 2 high dose molecules of lower OM quality (singletons -yl acetate, b-carotene), where 4 components were previously commercialized in the old ACES formulas, part way approaching, then current orthomolecular recommendations (several times /day & even more C???), omitted a known redox or biological couple with vitamin C (generating an unrecycled hepatotoxic metabolite) and omitted selenium, a proven, important factor for selenoproteins (critical enzymes like glutathione in the liver) in a selected, high oxidative stress population. A minor factorial pretrial (or two) with several biomarkers(as many as you can think of & implement cheaply - beg, borrow and otherwise, GC, HPLC, test substrates, etc), perhaps with RDA, 2-3g & 8-12g C/ day ditto say 200 mcg organo Se added might have been interesting & cheaper. This 2 component b-c/"E" test just is not relevant to orthomed's protocols; insistently used this way it's a hatchet job with a doppelganger. Shut off the water and air on any patient, and you can "prove" food is useless, too.--TheNautilus 23:16, 23 October 2006 (UTC)

It's not so much about OM vs. conventional med. A wise man once said that there are only two kinds of medical treatments: those that are proven to work, and those that are unproven. The treatments that OM advocates are, by and large, unproven. You argue that "Practicing doctors passively waiting to be spoon fed the answer is wearing thin with the public." Perhaps I don't have my finger on the pulse of the vox populi like you do, but I think that physicians prescribing unproven treatments would wear thin even faster. It's easy to push for that kind of thing when you have no accountability. When was the last time an OM practioner was sued for a missed diagnosis, or an improper treatment, or a bad outcome? Physicians have a ethical and legal responsibility to practice within the bounds of what's proven to help the patient, and they're accountable to a much greater degree than alternative practitioners. I'm not debating the fine points of tocopheryls, I'm just asking for proof of efficacy, or at least the recognition that such proof is important. If you're waiting for "conventional medicine" to spoon-feed you the perfect trial of the perfect mix of vitamins, then it may be a long wait. MastCell 17:27, 24 October 2006 (UTC)

"easy...you have no accountability" Maybe a pittance. As insignificant & miserable as they may be, we still value our health & our lives.

"...unproven..." not for a lack trying, but I'll see what I can arrange

"...prescribing..." it would be a tremendous service advance if many doctors were merely knowledgeable (or accepting) in current therapeutic nutrition and were willing to apply it, or, require it of their dieticians and associated hospitals...

Ok, I've tried to identify what doesn't constitute an accurate description of orthomed here and, moreover, why. I will note that the conventional medicine presumptions of what "might be" orthomed in their mind & less safe are noted generally in the "Rare risks...megadose...CHD...liver toxicity..." sentence despite being pretty much about the earlier industrial vitamin versions (K₃, D₂, strong/wrong acid salts of some B's, etc), unknowing 40s MDs, industrial accidents, & perhaps, overeager illiterati, are not orthomed based protocols. I am going back to edit mode and will try to take it slowly. Hopefully this discussion provides better b/g.--TheNautilus 18:30, 24 October 2006 (UTC)

OR

The "relationship to mainstream medicine" section is starting to fill up with original research. I placed citation-needed tags behind a few statements; we need to show that others have actually made these claims (besides those of us editing that article). I inlcuded a cite-needed for this sentence: "Long commercialized megavitamin formulas, "ACES", that also include vitamin C and selenium to recycle the first two antioxidants and aid liver peroxide detoxification, were not tested or measured." If it's going to be included, we need a citation where this criticism has actually been raised. MastCell 19:05, 24 October 2006 (UTC)

I'll cite it, I would more appreciate your editorial thoughts on the wording before I invest too much, though.--TheNautilus 19:28, 24 October 2006 (UTC)

Well, I'm not a huge fan of the above sentence. You make the point that the studied compounds are not what an OM would use. Specifying an alternate compound you believe should be tested sounds like OR, although if you find a source (outside Wikipedia) recommending its use, that might be acceptable. For the other stuff (particularly statements about "preferred OM therapies", I don't have a problem with the wording; just would like to see a source. MastCell 20:09, 24 October 2006 (UTC)

They are substantially referenced in the Bibliography texts & External links e.g. JOM & Saul's DYS (& FYD).--TheNautilus 20:20, 24 October 2006 (UTC)

The biblio is great, but specific claims need specific citations (source, page #, etc). Please see WP:CITE for policy guidance. As an article on a scientific topic, a scientific referencing style should be used (eg footnotes after specific claims), rather than a general bibliography. MastCell 22:48, 24 October 2006 (UTC)