Sep 24 2012
News flash! Doctors aren’t all compliant pharma drones!
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[...] I found this interesting: David Gorski at Science-Based Medicine discussing a study examining doctors' attitudes to drug company-funded studies. [...]
As I sit here downloading my iOS 6 operating system (into my now hopelessly dated iPhone 4S) and wondering if I will regret the map app coming with it), I am feeling very tired from staying up very late to try to write an effective response to the enormous load of stinking dingo kidneys that followed an open letter from the Mayor of Portland (Oregon) who issued said letter prior to his vote to add fluoride to Portland drinking water.
I was alerted to this letter by our good friend Dr. Barrett of Quackwatch. The letter included intelligent, respectful, and documented responses to at least a dozen (mostly completely whacky) objections to fluoride, many of which probably originate from places like NaturalNews.
The comments that followed were overwhelmingly full of bad (really bad) grammar and even worse levels of critical (or any) thinking. The overuse of exclamation points, truly filthy language, and outright threats were at high levels. Long spam type of posts were double and triple posted, some using the title doctor without saying of what. One ends up hoping that the addition of fluoride will do something about the insanity that grips some portion of the population of my former home city. I remember having to get the fluoride pills and pay for lots of supplemental treatment at the pedodontist for four kids due to this lack of modern public health policy in Portland.
The overriding complaint was the “health freedom” gambit, but “pharma shill” was right up there as well. Dentists, of course, (“mainstream” ones, anyway) are an evil cabal (is that redundant?) of pharma and government overlord shills. You will be happy to find out that fluoride is a DRUG and about to become a forced medication that will be poisoning the water supply against the will of the people, who were cruelly and surreptitiously denied the right to vote directly about the matter! They are getting ready for a referendum and they only need 20,000 signatures–but only have 30 days to get them.
A few brave souls complimented the Mayor on his research and ultimate decision favoring science, but they were exposed quickly as mindless nazis obviously in the thrall of….well, you know the drill. I’m just so glad that my grandkids are across the Columbia in long-time fluoridated Vancouver, Washington.
So I’m glad to hear that doctors seem to be up to speed, but we have a ways to go with the public. I would like to know what percent of the Portland population this response represents? Dr Crislip, can you offer any insights?
I’ve read Goldacre’s article in The Guardian (actually before I came across this here on SBM) and have added the book to my Amazon wishlist.
I personally find the issue to be daunting. We know pharma companies engage in unethical practices, don’t publish or make available negative data, hide side effects, and play games with regulations and laws (including ghost writing and studies in devolping nations). But, as Ben says, we don’t know how much and how often they actually do this. We do know that drugs work – and often work incredibly well. That statins are effective in reducing CV mortality is nearly a definite at this point. They have been around long enough, have enough non-industry studies, and massive meta-analyses. But for other drugs, especially new ones, how much don’t we know about the potential side effects and the true effect sizes?
I reckon that the level of skepticism – in terms of changes practices and giving drugs – is probably appropriate. I certainly don’t think that you can argue it is too much – we are forced to being overly conservative because we simply don’t know what we don’t know. In a hypothetical scenario where we are omniscient and know exactly what is being with held and manipulated then it can be asserted that we are too skeptical or not enough. But in the face of simply not knowing if these transgressions are merely the tip of the iceberg or most of it (nor even how big the iceberg is) I think it is hard to say we are being too skeptical.
For argument’s sake I’d ask what about being even more skeptical to make the pharma companies earn back our trust as a necessary step to protect their bottom line? If we don’t prescribe, despite them spending gajillions of dollars on studies because we can’t trust them, then we shift their bottom line and the means to get there. I know it is vastly more complicated than that, but it seems like a start – something our professional associations could get on.
From my (novice) perspective, I would view pharma funding as providing me two things. A reason to read the study much more carefully and (with the possible rare exception) never making the drug my first or even second line choice. I may conclude that the study was still reasonably done (though Goldacre demonstrates how apparent effects can be completely manufactured) and that the drug may be effective for a condition. But I cannot trust that I know the full picture of the risk nor the true magnitude of the benefit. To make something first or second line I would need to be able to make an assessment on that. Once you get to 3rd line drugs you are already in a situation where risks become much more likely to be outweighed and thus it becomes an easier choice to make.
No matter how one slices it, however, this is an area where reform is certainly needed and scientific integrity and intellectual honesty need to rule the day. Unfortunately the harms these days are not as clear cut as the were back in 1905 leading to the creation of the FDA in the first place* so I am less hopeful that a massive uprising of the people will clamor for this change. That leaves it to us to push the issue as best we can.
*I recently toured a pharmacy museum in my current town of residence. It is the oldest pharmacy in the US featuring the first ever licensed pharmacist. It was impressive to see how far we have come. My better half was stunned out how things used to be and was in thrall remembering the various things I tell her about in my own studies. An interesting example was a pacifier (or binky, if you prefer) for babies with a cleft lip… made out of lead. It was noted at the time that lead seemed to quiet the babies down better. As did the heroin/opium colic tinctures that were used. We forget just how far we have come in such an incredibly short time and, to use an expression from my current locale, have probably grown a bit too big for our britches. I suppose though, that when people think statements made by Presidential hopefuls “all the way back in May” is ancient history not pertinent to the discussion 100 years seems like geologic time. Maslow’s needs have been met in spades and the decadence of a 140 character world has spoilt the conversation. I think, however, that overall we are still progressing in the right direction… we just need as many as possible to keep up the solid work.
I just figure every study in the real world is half as good as reported; the big pharma/bias discount I apply to every literature purchase. Makes the results of SCAM studies particularly unimpressive
I persist in believing that a better system would involve the money spent by Big Pharma to conduct trials of new drugs being given to a third party (almost certainly government) who would run the trial instead, publishing all data freely. If you could convince the FDA and other regulators that drugs could only be licensed by trials passing through such a system, all the better. You would have to create another layer and system of bureaucracy, but the value of a third-party running actual trials and publications would probably more than offset this.
@Janet Camp
“I’m just so glad that my grandkids are across the Columbia in long-time fluoridated Vancouver, Washington.”
Perhaps you have stumbled onto a previously unknown benefit of fluoridated drinking water: improved mental health. As you certainly know the unofficial motto of Portland is, “Keep Portland Weird” while the unofficial motto of fluoridated Vancouver, WA across the river is, “Keep Vancouver Normal.”
Kind of makes one wonder…
I just figure every study in the real world is half as good as reported; the big pharma/bias discount I apply to every literature purchase.
Except for my studies. My studies are always more awesome than what appears on the pages of the peer-reviewed journal.
@windriven
Ha! That’s pretty much what my comment said at the end of all the craziness posted in response to Mayor Sam Adams’ letter. I’m so old now that I only remember Portland being called “The Rose City”, and Vancouver was, well, just Vancouver–where you had to pay sales tax.
Where did all these people come from? Obviously, there’s always the inflow from California, but a surprising number of the “weird” come from…drum roll…Michigan, Minnesota, and Wisconsin. So there you have it–proof, proof I tell you, that fluoride causes insanity once you withdraw it from the water supply–or withdraw the users from the treated water. So stay “normal” in Vancouver.
Just an afterthought thought–if the fluoride is at .07 per million, is that homeopathy (or as good as version as some of what is marketed as such)? Kinda goes with your observation WD. So wouldn’t whatever evil effects are being subscribed to fluoride have the opposite effect on the population? The Mayor also promised (and gave evidence) that the fluoride won’t affect the beer–and if you believe that..well, you really are an evil pharma shill.
I totally apologize for digressing.
I have a question I feel is legitimate regarding the pharma shil gambit. I’ll start by prefacing the fact that Dr Gorski wrote another entirely awesome screed on this study. However I heard something, so yes it is a rumor, so humor me., and please only the doctors chime in on this one as they are the ones to know. Do doctors ever receive kick backs or compensation for prescribing medications from the pharmaceutical companies?
This is not to be confused with the practice of paying Dr’s for lecturing about a pharmaceutical, nor is it a to be confused with gifts etc. Can GP’s actually make money off of prescribing a particular agent, be it beta blockers, statins etc.?
[...] Science-Based Medicine » News flash! Doctors aren’t all compliant pharma drones!. Again, from one of my favourite websites, a report on how doctors perceive results of well designed studies funded by pharmaceutical companies. They are often more sceptical - unsurprising given some of the bad behaviour of some pharmaceutical companies. However, this may mean that some doctor’s are not giving their patients the best possible treatment. Good advice: wait for 2 or 3 replications. Share this:TwitterFacebookLike this:LikeBe the first to like this. This entry was posted in Health, Health Care, Medicine. Bookmark the permalink. ← Whooping Cough Vacines [...]
@Purenoiz,
No one ever offered me a way to get kickbacks for prescribing a drug, and I’ve never heard of anyone I know being offered any kind of kickbacks. I’ve read about accusations, but if it happens, it’s clearly illegal and is prosecuted.
Some issues, from the perspective of a scientist:
Most alternative medicines are “evidence based” to some degree, unfortunately knowledge of the placebo effect is fairly recent, the statistics required for good trials can be a little bit complex, and isolating/controlling variables is often a challenge. We do a better job of this than we used to, but I see so many horribly designed studies that I hesitate to say we’re good at it yet. “Alternative” medicines that have survived for hundreds (or even thousands) of years do so because people see value in learning them; I hesitate to dismiss hundreds of years of trial and error until a significant body of well designed and executed research weighs in to the contrary. There are a few cases like crystals, “energy” massage and homeopathy that really have no conceivable mechanism of efficacy where I agree with you completely.
The publication bias is amplified by the amount of money available to research something. The pot for CAM is a lot smaller. If you accept a p value of 0.05, and pharma funds 20 studies for every CAM funded study, of course they are going to come out looking pretty good. I’m not saying this is the only factor, but it should be kept in the back of your head.
At the end of the day, the only thing that should matter is “is your patient getting better”? If a particular treatment is very effective at eliciting a strong placebo response for whatever reason, does that make it less valuable than a non-placebo treatment with more side effects? Are we actually advancing the state of medicine if we destroy people’s perception of the placebo treatment? What about when we say that we have no reason to believe a medicine works, just because no clinical trials have been performed with it, despite hundreds of years of continued use? Perhaps we should instead say we have no scientific evidence showing its efficacy is due to the placebo effect.
@Purenoiz,
Way way back in about 1974 in the summer after completing general surgical residency and fellowship but before going on active duty in the US Navy I worked as a GP/GS in a small town in rural western Washington covering a physician taking a well deserved 2 month vacation. One particular pharmaceutical rep was all over me: there was no talk of kickbacks, but everytime he learned from the hospital’s pharmacy that I had prescribed one of his company’s products he would come by bearing gifts: he would invite me to dinner at better restaurants, offer me tickets to professional sports events in Seattle, and even offered to broker a discount at a nearby luxury car dealership amongst other things. He had a great gift of gab and it was very enlivening to talk to him. I never accepted. If I had stayed there longer especially into the dark rainy Pacific northwest winter I might perhaps have gotten soft around the principles and justified accepting some of these “gifts” as a diversion. I was never in a rural setting again so I do not know if that sort of thing continued, however no one ever blatantly offered me any benefits besides ballpoint pens during 33 years in group practice in San Diego. Sigh.
Hi Nathan,
Are you a newcomer to this blog? If so, I suggest reading some of the back-links as there are numerous objections to some of your points. For instance, “is your patient getting better” is essentially what sustained nonscientific medicine for years. It’s patronizing and unethical, harkening back to the days of paternalistic medicine. The use of unproven “medicine” is, if harmless, still a waste of time and money and often serves to introduce patients to the CAM mentality which is itself based on a negative assertion – opposition to real medicine rather than evidence-based demonstrations of efficacy. CAM can lead to rejecting conventional treatment, often its most dangerous effect, and that can kill. For instance, see this post on SBM.
You could also try searching for the word “shruggie”, which seems to be your position. Though far better a position than actively promoting CAM, it still presents risks to patients.
Ah, the argument from antiquity. This one is fairly easy to deal with using a counterexample or two (or three). Let’s see. What should I start with first? Oh, I know: Bloodletting. Bleeding for virtually everything that ailed anybody “survived for hundreds (or even thousands) of years do so because people see value in learning” it. Indeed, bloodletting only fell into disfavor maybe 150 years ago at the most, maybe even more recently. Now, how about another example? I know the perfect one: Homeopathy! Most homeopathy is nothing more than water or the diluent used to dilute a homeopathic remedy into nonexistence, and it’s persisted for well over 200 years now. How about another example? Hmmm. Faith healing. Yes, faith healing has been around for hundreds, if not thousands, of years. Indeed, one alt-med that’s currently popular, namely reiki, is nothing more than faith healing. (Don’t believe me? Substitute “God” and the “power of God” for the “universal source” and the “healing energy” that comes from that “universal source” in reiki, and the resemblance is unmistakable. Reiki is faith healing that substitutes Eastern mysticism for Christian beliefs as its basis.)
So, here’s the deal. Just because a treatment or type of medicine has existed hundreds or thousands of years does not mean it must have some value. There are lots of examples of medicines that have been around that long that clearly do nothing or even cause harm. In other words, the argument from antiquity is a bad argument.
I think one of the points Nathan was trying to make is that lack of evidence does not equal lack of efficacy, especially given the global difference in research funding available. Of course, historical use of something alone is not enough to justify using it at the expense of a current research proven treatment, especially the more serious the health condition is. Historical use/empirical evidence of something is just part of what makes up the whole context of human use – or, put another way, the bottom of the evidence based pyramid for “what works”. In cases of say, treating cancer, it would be crazy to rely on historical use alone, but in other examples, say you’re experiencing indigestion with gas, bloating, cramping – you’ve read that peppermint and fennel have long been used for that, there’s some small studies reinforcing the historical use, there’s a plausible mechanism of action, it’s not a life threatening condition, etc. In a case like that, why would I wait for an RCT to tell me whether I should try it or not?
I think part of the problem is that too many completely disparate things get lumped into a CAM umbrella when they have no relation to each other and that too many CAM “things” attempt to treat or claim to do things they are not able to. Personally, my background is in herbal medicine and related research and I know the importance of not overstating what it can and can’t do. I do like the position of many here that there is no such thing as CAM, just medicine that works and medicine that doesn’t (or hasn’t been proven to yet). A lot of that position hinges on what you define as “medicine” though. I wouldn’t call food medicine, although it’s obviously crucial to good health. If you define medicine as simpy agents that treat pathologies effectively, then, while it is succinct and convenient, reality isn’t as black and white as that and you have sub-clinical pathologies – you don’t go from 100% healthy to full blown disease state – it’s on a spectrum. A lot of herbs and supplements do their best in that middle ground between food and drug, between full health and full pathology – thus the structure/function claims that they make within the regulatory framework in North America, Europe, and Australia/NZ.
Harriet and Laproxdoc,
Thanks for the heads up. I will try to get some clarity from my girlfriend, she interviews doctors to see if they are a good fit personality wise, and that they have her best interest at heart.
Just out of curiosity Harriet, what would they be prosecuted for?
Dr. Gorski, don’t forget simple magic. Ancient Egypt, which had a relatively highly developed medical system that modern research indicates might actually help in certain circumstances, was based equally on specific interventions (raw meat on wounds to speed clotting, trepenation) and prayer. In fact, prayer probably has the longest documented history of any medical intervention. I forget, is there evidence it works?*
It’s not even an argument – it’s a fallacy.
Robb, the whole point of this blog is that prior probability should underscore things like where we should put our scarce research resources. Realistically, we can pretty much dismiss anything from before the germ theory of disease and microscopes. Herbal medicine is pretty much the one CAM modality that is seen as having any merit, but as has been said here many times it is redundant to pharmacognosy. It still isn’t even medicine, since it’s still mostly old wives tales and unproven assertions. Until a specific herbal preparation has undergone scrutiny via pharmacognosy, you still don’t know whether you’re doing any good or just wasting time and money. And bundled with that waste must be recognition of the company kept by herbal medicine – if you believe in it, you’re more likely to endorse or recommend things substantially or actually worthless things like homeopathy, acupuncture, reiki, laetrile, Hulda Clark’s “zapper” and other such nonsense. As said by Dara O’Brien, we tested it and what worked became medicine. Everything else is a bowl of soup and some potpourri.
*I kid, I know it doesn’t.
@purenoiz,
“what would they be prosecuted for”
I think it is the drug companies that are prosecuted. Doctors could be disciplined by their medical boards for unethical behavior, but that’s not likely to happen.
This rather misses the point. Few people would argue that it’s unreasonable for you to try it. What we do argue, however, is that it is grossly inappropriate (some would say outright fraud) for someone to SELL peppermint and fennel as cures for such symptoms without actual evidence.
William: “It still isn’t even medicine, since it’s still mostly old wives tales and unproven assertions. Until a specific herbal preparation has undergone scrutiny via pharmacognosy, you still don’t know whether you’re doing any good or just wasting time and money. And bundled with that waste must be recognition of the company kept by herbal medicine – if you believe in it, you’re more likely to endorse or recommend things substantially or actually worthless things like homeopathy, acupuncture, reiki, laetrile, Hulda Clark’s “zapper” and other such nonsense.”
If you think herbal medicine is mostly based on old wives tales, you have never really looked into the subject.
I also totally disagree with your “guilt by association” generalization. How did you come to that conclusion? Who is this “herbal medicine” entity you speak of that always acts and thinks in the way you attribute? I’m convinced of its value but I think homeopathy is hokum. I know it makes life (and arguments) easier to paint with broad strokes and stereotype but reality isn’t like that.
Scott: Fraud? The point is, there is evidence in many cases. The level of evidence required before you accept it can be debated but in my specific example, the current level of evidence is already widely accepted as sufficient in order for it to be sold.
The current level of evidence is “accepted as sufficient” because Big Herb bought themselves some senators to get the DSHEA passed. In no rational or reasonable sense is it anything other than fraud in the overwhelming majority of cases. Even in the cases where there is some evidence of efficacy, it’s just crazy to prefer an impure preparation of unknown concentration (an herb) to a standardized purified known dosage (a pill).
@Robb,
“If you think herbal medicine is mostly based on old wives tales, you have never really looked into the subject.”
You misinterpreted what he said. Old wives tales are little more than anecdotes and they don’t become data until they are tested. Some old wives tales pan out, others don’t. He said herbal medicine is the one CAM modality that has merit, but that it is redundant to scientific phamacognosy.
And the “guilt by association” is obvious: CAM lumps all its modalities together under one umbrella.
@Scott:
That goes for supplements, as well. My wife prefers to take an “organic, whole foods” prenatal vitamin as opposed to the standard one. Not only does it cost 3x as much for the same number of pills, but you have to take 3x as many pills to get the same amounts of the vitamins and minerals. Somehow, all that impurity is “better” because its “more natural”. In what universe does that make sense?
Added a minor edit there. The fact that a naturopath will inject homeopathic preparations into acupuncture points is an astonishing exercise in double-think or lack of thought.
Robb, you may be different, you may be very conscientious (if I recall your comments correctly, you have stated your own concerns about TCM preparations, the species, preparation and packaging of specific compounds and the like), but the very nature of your profession is substantially unproven. The very fact that you feel the need to separate yourself from others in your profession, that you feel the need to take extra steps to ensure your products meet the safety and efficacy needs of your clients that are above and beyond what most others require – this is evidence and a tacit admission that your profession is based on dubious claims and often worse science. Good for you for taking these extra steps and incurring what is doubtless extra expense and bother that most clients probably don’t notice or appreciate. But a pharmacist doesn’t need to take them because 99.9% of the time he knows what he’s getting, what it’ll do, and what kind of quality control is involved.
None of this applies if I’m mis-remembering your comments. I hope I’m not, because it indicates you are both thoughtful and conscientious – but science and medicine rest on premises tested against evidence, not anecdote and old stories. Herbal medicine is at best suggestive, believing historical use is proof is simply wrong.
Also, everyone should click on Dara O’Briain’s youtube video. It’s tops.
Scott,
So what you are saying is that you have reviewed the entirety of the evidence for herbal medicine and it is in all cases so lacking that the only way it can be legally sold is by a couple senators being bought out? Really?
I’m not in the US myself but that sounds like the same kind of conspiracy theory regarding the revolving door between the FDA and pharmaceutical execs. I don’t know…maybe both cases have some degree of truth as far as influence.
In any case, I don’t believe, and other regulatory agencies around the world (not just in the US) don’t believe, that herbs require the same standards, or should be treated the same as, pharmaceuticals. Part of the history of use thing is that they have been in our diet for that long, which goes a long way towards establishing safety, rather than some novel unknown compound. Secondly, they are not intended as primary treatments for serious diseases so, given their safety, a lesser level of current evidence is considered acceptable. Do I require an RCT on broccoli before I’ll eat it and consider it nutritious? Do I expect food manufacturers to do bioavailability studies to prove the nutrients listed in their nutrition facts panel are actually well-absorbed? No. Do I want some new compound that is supposed to save my life from cancer and comes with significant side effects to have a high level of research based efficacy? Of course. Do I expect that same level of rigor for something I take when I’m constipated, have some arthritis pains, insomnia, or indigestion? No. Why? Because I’m dealing with a known substance that is safe for something that is much less of a critical health issue, I am willing to accept a lesser level of evidence – not no evidence – but a lesser level.
As far as an “impure preparation of unknown concentration” goes, maybe you are not familiar with the subject. GMP and government regulations require purity and known concentrations. If someone purchases an herbal product that is adulterated, uses a wrongly identified herb or the label doesn’t reflect amounts actually in it, then that is illegal and the means are there for them to be removed from the market. In the vast majority of cases, the purity and concentration are not an issue. Even making a cup of tea, you know the concentration of loose herb to water as a basic starting point. Standardization is a different subject and herbs differ greatly to drugs. Herbs work by way of multiple constituents working together (synergy) and isolating a single constituent to standardize doesn’t always produce best results. There have been some interesting studies done already to try to tease out exactly what is going on synergistically. Anyway, I suspect I’ve probably overstayed my welcome in dragging this off-topic so I’ll leave it at that.
William,
While I appreciate your sympathetic tone, I suggest you stop making assumptions. You are shooting blanks. I do not see clients. I am not pretending to be a substitute doctor. I am involved in research on herbs though and am very familiar with the body of knowledge and with government regulations regarding their sale and use. Also, as I’ve said already, believing purely in historical use is not what I’m advocating. To repeat, empirical evidence is part of the pyramid of evidence, but it is the lowest level. It suggests there may be something to it, but it “needs more research”.
More precisely, the entire concept that herbs can somehow simultaneously BE medicines, but not subject to any standards of evidence for safety and efficacy, is so mind-bogglingly ludicrous that it can only happen via the purchase of favorable legislation.
If pharmaceutical claims are being made for them, then they most certainly should.
If you are going to claim that broccoli cures cancer, then absolutely you need robust RCTs before you can sell broccoli with that claim attached.
Again, we’re not talking about TAKING it, but SELLING it by making claims that are unproven.
Even if it’s 100% pure plant, it’s impure and of unknown concentration. In many cases no active ingredient is even hypothesized, much less known, so there is no way whatsoever to have any meaningful standard.
[citation needed] Actual synergy is VERY rare, and even in the cases where it exists, it’s incredibly unlikely that a plant just happens to have the optimal ratios of various ingredients. Yet another reason herbal medicine really has no place in the world other than as a source of investigational leads for pharmaceuticals.
Scott,
What do you mean “even if it’s 100% pure plant, it’s impure”? How does this even make sense?
With most herbs that have had even preliminary research done on them, the ingredients are well known and most have a number that are considered most “active” and used as a basis for standardization. The German E Commision monographs or Dr. James Duke’s phytochemical database at the USDA agricultural research website are two examples off the top of my head that deal with detailing active ingredients. Any good reference book like Principles and Practice of Phytotherapy by (Simon Mills & Kerry Bone; pub. Churchill-Livingstone in 2000) does the same.
Ah synergy vs. reductionism…far too big a topic to cover in a reply to a blog post on a completely different topic. In many scientific fields, reductionist “silver bullet” thinking is giving way to more complex, systems based approaches and I don’t think pharmacology is any different. I still chuckle when I read some of the simple minded cautions in pharmacy texts or databases regarding herb-drug interactions. For example, that red clover should not be taken with blood thinning medications because it is a source of coumarins. Never mind that di-coumarol was originally discovered due to sweet clover being spoiled with mold and that coumarins do not act like di-coumarol in any way. But I digress…your point was, I think, that “synergy is rare and/or unlikely to occur, therefore, herbs should just be raw materials for new drugs”?
Synergy is quite common, not rare. Here are some citations concerning plant synergy if anyone at this point is still remotely interested:
E. M. Williamson. Synergy and other interactions in phytomedicines. Phytomedicine, Vol. 8(5), pp. 401–409.2001
Spinella M. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev. 2002 Apr;7(2):130-7. Review.
Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals.
Phytomedicine. 2009 Mar;16(2-3):97-110. Review.
Ohno T, Kita M, Yamaoka Y, et al. Antimicrobial activity of essential oils against Helicobacter pylori. Helicobacter. 2003;8(3):207-215.
Generally, standardization and isolation of compounds leads to increased toxicity and side effects – also increased efficacy in some cases of course too. Synergy demonstrates that more can be made of with less though. Less of the actives are needed because their effects are boosted by secondary constituents. I probably don’t need to explain that. Pharmaceutical approaches are recognizing the importance of synergy as well and that the reductionist, single molecule approach isn’t always best when it comes to dealing with malaria and bacterial infections and cancer for example. I really do apologize for taking this off on such a tangent, but it came up and it’s a fascinating topic to me.
No matter how rare or common synergy is, it can’t be assumed, but must be tested for in each individual case.
Scott,
“Few people would argue that it’s unreasonable for you to try it. ”
Why would you “try it”?
If there is no evidence that it works, why would you “try it”?
Why would you not use something that does have evidence that it works?
Someone once asked me “but have you tried it”, and my response was, “you can’t see if something works by trying it, you have to do a clinical trial”
I am extremely tired after my second 14 hour day in the PICU so I simply don’t have the energy to respond in full, but suffiice it to say Robb is quite off the mark. As one small example:
Complete bollocks. Perhaps you would like to cite definitive and specific examples of drugs that become more toxic and have increased side effect profiles by purifying them. Perhaps you’d like to discuss vancomycin which still has a bad rap for being nephrotoxic because of impurities in the manufacturing process in the 60′s which no longer exist because the drug is now more pure. But, since this is a general effect you should have no trouble delineating the myriad drugs which follow the opposite pattern.
Next up we have:
Because, Robb, a plant has (to use the technical term) a bajillion compounds in it. Of varying amounts based on soil composition, environment, season, and specific species and subspecies. The vast majority of which are uncharacterized in their action and often difficult if not impossible to detect. So 100% echinacea or gingko or fennel or fenugreek or whatever is still an utter grab back of…. impurities.
But, as we can see, you are clearly an herbal expert well versed in the science of the matter.
Lastly:
Once again, clearly an expert deduction. Because when gingko is recommended for use in memory improvement that is based on scientific data, not wives tales. Same with saw palmetto for BPH, black cohosh for menopause, echinacea for colds, and feverfew for headaches. Oh wait. Those were all used for those indications prior to actual scientific studies demonstrating that they don’t work for those indications.
The fact of the matter is that the vast majority of herbal use is purely old wives’ tales – unless you would like to demonstrate a corpus of scientific data on herbs that pre-dates their usage for such indications (i.e. nobody heard of feverfew and studied it and discovered it worked well for headaches and then was advertised as such). Oh yeah, that does exist – it is called pharmacognosy and is part of the high throughput screening used to discover and create…. purified pharmaceutical agents!.
I am exhausted so I bid adieu but I couldn’t resist going after such bad argumentation and clear lack of understanding… and I barely scratched the surface with those mere 3 examples.
It’s actually a modality that isn’t that uncommon in woo land. It’s called homeopuncture. I kid you not:
http://scienceblogs.com/insolence/2010/02/26/your-friday-dose-of-woo-how-do-you-make/
@nybgrus,
I know a lot of herbs that have actual uses and effects. Cannabis, peyote, opium, coca leaves, hemlock, just to name a few.
@weing: fair enough. But what were they used for vs what does the science tell us to use them for now? I never said none of the current uses stemmed from old wives tales. But it is by far a minority. And did they become more or less toxic as we refined them from raw form to pharmaceutical grade?
(I know you are playing devil’s advocate)
@nybgrus,
Isn’t it curious that none of them are found on the shelves?
It includes the actual active chemical(s), AND a bunch more.
No. Synergy is rare. AND herbs should be just raw materials for new drugs.
If anything, synergy makes standalone herbs LESS credible since it makes it even more vanishingly unlikely that whatever random conglomeration of stuff evolution happened to throw together for non-medicinal purposes can’t be improved upon by science. The idea that it’s even possible for herbs to have some kind of synergistic effect which cannot be replicated by isolating the active ingredients is straight-up false. 1+1=banana level false.
Williamson: Unfortunately I can’t access the full text; this is your only citation that looks vaguely credible based on the abstract. I do really wonder whether it deals with ACTUAL synergy or just “multiple active ingredients can stack.” True synergy means that there’s actual interaction where one ingredient improves the other’s effect. Multiple ingredients producing the same effect is just a bigger effective does, not synergy.
Spinella: Completely speculative that synergy MIGHT be relevant in some cases and should be looked for. Not evidence that it is “quite common.”
Wagner: Suggests that because herbal combinations are known to be more effective (gross begging the question), it must be synergy.
Ohno: Abstract doesn’t even mention synergy.
Still, synergy is a complete side question – since even in the cases where it exists, it provides zero rationale to use herbs.
Gonna need REALLY good evidence for that, since this claim can be paraphrased as “adding a bunch of completely random other chemicals reduces toxicity and side effects.”
Overall, I get the impression that you subscribe to the “God created herbs to be ideal medicines” philosophy as opposed to the reality that they contain whatever mix of chemicals evolution happened to produce – without selective pressure towards being effective medicine, so without any reason to believe any medicinal properties are more than coincidental. Is that so?
Apologies for the double post, but I wanted to add a brief summation.
In the absence of specific testing for safety/efficacy, selling an herb for medicinal purposes represents both false advertising AND the risks inherent in an untested drug.
If the active ingredient(s) have been identified, an herb is strictly inferior to a standardized, purified preparation of that active ingredient, due to variable concentration and potential effects of the other constituents.
ONLY in the case where proper safety/efficacy testing have been done, AND no active ingredient can be identified, might it make sense to sell an herb for medicinal purposes. As a short-term stopgap while the active ingredient is identified so that it can be sold in a properly standardized and purified preparation. I am quite skeptical that this category has any meaningful extent.
Not so much assumptions as vague memory, it’s quite possible I’m remembering someone else’s comments (might be skepticalacupuncturist, I think they said they worked in a TCM “pharmacy”).
At this point in the arc of knowledge and research, is historical use even part of the pyramid of evidence? You would probably be able to answer this question given your expertise, is it possible to look at the molecular structure of a compound and have a reasonable guess of its effects on the body?
But I stand by my point – historical use is of questionable use even for safety information, let alone efficacy (fava beans, which I hear are delicious when paired with human livers, can kill via favism but are a significant ingredient in many cuisines). I’d sooner use it to indicate if an herb would be good in a tea than I would to prevent or treat anything. Until a specific compound is demonstrated useful in treating a condition (at which point I’d much rather consume it from a vat than a root) I see it as an ingredient, not a medicine.
Your comment about empirical evidence is…curious to me. Even historical evidence can be seen as a type of empirical evidence, I’m assuming you mean scientific? Research?
Just noticed this today: http://archinte.jamanetwork.com/article.aspx?articleid=1357513
Scott: relating to your feeling on plants versus synthetic drugs, I am ok with broad spectrum standardized extracts at known concentrations, but you don’t seem to understand how difficult coming up with a synthesis is. Most molecules will have a whole host of structural isomers which can be formed which can have vastly different effects, and these are incredibly difficult to separate out in most cases. Beyond that, it is also incredibly difficult to get beyond 98% purity with synthesis/separation, and the impurities resulting from a chemical process can be quite nasty. Bottom line is that a water/oil/ethanol extraction is a safer bet every time.
Additionally, note that pharmaceutical companies don’t WANT to just make high quality plant extracts, they want to modify it into something they can patent. Sadly, because the majority of bio-active molecules are polycyclic structures with resonance stabilization, you usually can’t do too much modification as cracking the molecule apart often can’t be done in a controlled way. Most pharma modifications of natural molecules are the replacement of a hydroxyl side chain with a bromine or iodine molecule, replacing one ester with another, or protonating/deprotonating nitrogen and oxygen atoms, as these are all fairly easy to do.
I think if the vast majority of the institutional health care system didn’t treat people like walking piggybanks and pharmaceutical companies cared as much about people as they do shareholders and profits, you would have fewer people trying to avoid getting standard medical treatment. Don’t blame CAM because people don’t seek treatment through regular avenues, blame doctors, insurance companies, pharmaceutical companies and hospitals.
The way I undersatnd it, the majority of the modifications you describe aren’t just for patenting. They are attempting to find compounds that have a larger therapeutic window, and/or fewer side effects but still have the same desired effects. But, maybe I’m not cynical enough about “Big Pharma”…
@ Nathan,
“Just noticed this today:”
You apparently didn’t notice that both Dr. Gorski and Dr. Novella have already critiqued that study here on SBM:
http://www.sciencebasedmedicine.org/index.php/can-we-finally-just-say-that-acupuncture-is-nothing-more-than-an-elaborate-placebo/
http://www.sciencebasedmedicine.org/index.php/an-acupuncture-meta-analysis/
@Nathan,
Digitalis is a case in point. They didn’t patent Digoxin just to make money, but because the active ingredient, purified and with controlled dosage, was far more effective and safer than the herbal product. I hope you wouldn’t recommend digitalis leaf!
I’m a little late to the party, but my favorite example of “100% pure herb” that is most definitely not pure is red yeast rice, which is lovastatin plus nephrotoxins. Mmm… nephrotoxins. Nybgrus already called BS on the “purifying them makes them more toxic” statement, but seriously, that’s poppycock. Unless you believe in magic.
Also, I’m not a medical professional, but aren’t there plenty of instances where synergy in medication bad, because it is unpredictable? Like why, if I have pain, the doctor says, “No, don’t have some bourbon with your oxycontin because they synergize to depress your breathing,” rather than, “You’ll sure get more bang for your buck if you potentiate your opiates with alcohol.” Or other depressants, like benzodiazepines or barbiturates or whatever.
I’m happy that I recognized everything that was wrong with Robb’s posts, even if everyone else deconstructed them before I had a chance to help. Thanks for teaching me SBM!
@ Nathan:
As a chemist, I have some problems with what you have said here:
It’s hard, yes, but people are capable of pretty incredible things. Have you seen how many syntheses there are of strychnine? Strychnine! That’s one hell of a molecule, and plenty of people are like, “Yo man I got this, here’s another way to make it.” Honestly, I feel like “it’s too hard” is not an adequate reason to resort to using a mixture of compounds. I can’t think of a single pharmaceutical that is used as an extract because people gave up trying to purify it.
Yes, it can be difficult to separate stereoisomers, but if I said to my boss, “Hey man, these diastereomers are tough to separate, so this NMR spectrum I have here has both major and minor diastereomers,” he’d say, “That is unaccepatable you lazy sack of crap, get back to work.” And yes, impurities can be nasty, but that’s why you purify things and why we have the FDA to make sure that you did an adequate job.
No. Purifying it is better. How can you justify a mixture is safer? As an aside, extracts from plants are not always practicable, either. To use taxol as an example, even refining the active ingredient from the plant, from the bark of some yew tree in this case, was endangering the trees because stripping the bark killed them. So some clever person came up with a semisynthesis to make taxol from a compound that could be safely harvested from the leaves. There is no way that you will convince me getting a bark extract that kills the trees is better than a synthetic version of taxol. There are people with cancer who need taxol! It wouldn’t do anybody any good if the trees went extinct or there wasn’t enough to go around.
Also, like Harriet Hall said, digitalis. There’s more than one bioactive compound in digitalis. How can you say a mixture with uncertain proportions is better that refined, pure digoxin?
I think I (and others) have addressed why extracts, even “high quality” ones, are inadequate. Also, I call BS on the “with resonance stabilization” comment. I don’t think that means anything in this context, it’s just a way of explaining chemical behavior. I also reject your assertion that pharma companies market natural compounds that have alcohols replaced with alkyl halides. That sounds toxic to me. Can you provide an example? Furthermore, “cracking apart” a bioactive compound would likely totally change whatever activity it once had (even if you could do it in a controlled way). In any case, processes to produce natural products can be patented, so modification may be unnecessary and is likely unproductive anyhow.
I do not have the energy to respond to this part. I think the reality of pharmacy reflects that purified compounds are both viable to produce and better and safer to use. Anyhow, sorry for the jargon, everybody (David Gorski does it, too!).
nybgrus,
It’s ironic you chose Ginkgo biloba as an example because its use of the leaf for memory does not exist in traditional use – it began with research into standardized extracts in Europe. The only traditional use was of the nut in Chinese medicine for non-memory/cognition related issues.
Harriet,
Digitalis is a great example of where isolating and standardizing a drug from an herb improved safety by allowing for precise dosages and avoiding toxicity. It’s more of an exception than the rule though. As far as I know, Digitalis was never used as a plant by herbalists – they used Lily of the Valley (Convallaria majalis) instead. Salix alba to acetylsalicylic acid and cannabis sativa to Marinol are some counter examples though where isolating and standardizing leads to side effects/different effects not present in the whole plant.
@NathanAlexanderRice:
It sounds like you have learned a lot of fancy words. If only you actually knew how to apply them.
First off, non-sequiter/strawman. What does difficulty of synthesis have to do with anything about the discussion. And yes, it is difficult – that is why there are entire undergraduate and graduate degrees in it. Do you have any idea how difficult it is to launch a human being into space and return him/her safely?
Yes, and every med student (should) know all about enantiomers. And how difficult – yet quite possible – they are to isolate. Xopenex for example. But furthermore, one should also be eduacted enough to know that different enantiomers tend to act in an “effect – no effect” sort of way. In other words, one enantiomer has an effect on the body and the other has zero. This is due to the stereospecificity of enzymes and molecular receptors and has, simply by chance, happened to evolved a dextrarotatry chirality (aka right handedness). That is why D-glucose is what we eat and L-glucose would have no metabolic potential. It is not, as you imply, that commonly multiple enantiomers of the same molecule would have disparate effects and thus be difficult to control the effects of synthesis. And lastly, I’ll point up to my above comment – controlling chiral centers in synthetic chemistry is the name of the game.
Really? That’s funny, because I consistently managed to get 97-99.8% purity in my synthetic chemistry courses. As an undergrad. Yes, some are much more difficult. But once again, a strawman that has nothing to do with why an herb would be more efficacious than a purified drug. Because even if it is less than 98% pure, that is still a lot more pure than an herb.
oh wait, you’d argue:
Which is a bollocks blanket statement. They can be. But, thanks to the FDA, they aren’t. Or, in the rare cases they are, it is known and thus a risk:benefit can actually be done to determine if the severity and prognosis of illness warrants exposure to those nasty wasty chemicals.
As TheDave pointed out, the vast majority of molecular modifications are to reduce side effects, increase potency, increase the therapeutic window, and favorably alter the pharmacodynamics. And that’s a good thing.
Bollocks. See first comment.
The first (though only partially) correct thing you’ve said. Though for the very wrongest of reasons.
@Robb:
It’s ironic that your only rebuttal is to pick a completely irrelevant nit. (wait, is that actually irony? It’s something anyways…)
@weing:
Now, now. That is not true. Go to California and you can find all the marijuana you want on shelves! It is a shame they pulled coca leaves and heroin poppies from my locals Lowes Garden Center though.
@gears:
Seems we posted at the same time. All I can say is – high five!
@ Robb:
I don’t want to come across as hostile, because I really do want to convince you that pharmaceutical grade compounds, regardless of source, are superior to mixtures in the form of extracts or whole herbs. So here’s trying:
I don’t think it matters whether the use was traditional or not. A big part of this blog is how traditional modalities should not be privileged by virtue of being traditional, because it’s so easy for people to fool themselves into seeing efficacy where none exists, and that’s why clinical trials are required. Furthermore, traditional modalities that fly in the face of all evidence should be discarded without bothering to do clinical trials, like homeopathy. Others have already expressed how while there is reasonable prior probability for some herbs to have a use, unlike most of CAM, it’s still better to find an active agent and use that, which is why everyone keeps advocating for pharmocognosy over herbalism.
Again, I disagree with you here. The rule is that isolation and standardization improve safety. It’s tempting to launch into a laundry list of pharmaceuticals derived from natural sources, but I’ll just discuss opiates for the moment. There’s a reason that people don’t use just opium or laudanum anymore, and that’s because it’s difficult to dose accurately. Furthermore, by purifying morphine and other constituents in opium, and making derivatives, you have painkillers that range in strength from codeine to heroin, novel drugs like buprenorphine, antagonists like naloxone and cool names like thebacon. That gives you such a bigger and better pharmacological toolbox than just straight opium.
I also think your counterexamples are rather dubious. What side effects are present in aspirin and not willow bark? So far as actually using willow vs. aspirin is concerned, I can’t imagine a doctor telling someone to chew on yea-much willow bark to get the correct salicin equivalent of the (amusingly specific) dose of an 81 mg baby aspirin. There’s a reason to isolate and refine drugs.
I’m not sure what you’re referring to with cannabis vs. marinol. Yes, I’ve heard that CBD modifies the effects of THC, and that smoking it is better for a nauseated person that trying to eat a pill. Maybe this would make it almost a legitimate exception, but even so, that’s only two compounds together, and if that’s the case then there is no reason you couldn’t find a standardized ratio and dose. Maybe you could throw them into an inhaler or something. Point is, there is nothing magical about whole herbs vs. isolated compounds.
I will concede that I prefer the hot water extract of coffee grounds to caffeine pills.
@ nybgrus:
Holy crap. High five, indeed!
just goes to show the difference between knowing just enough about organic and synthetic chemistry to string a grammatically correct sentence together versus actually knowing how to do organic and synthetic chemistry. I actually almost became a chem major in undergrad until the lure of squishy science won out and I did evo-bio instead. However, along the way, I did a fair bit of chem and have the highly nerdy distinction of being the only student in my class to have succesfully synthesized – and purifed – a Grignard reagent.
as for:
That is because it is 25% of the previously standard 325mg pill and for a while it was easy to quarter up tabs and thus the studies were done at that level and then when efficacy was demonstrated began to be manufactured at that dosage. I think maybe kids had something to do with it as well but I’m not sure.
Awww. Give the man a beer
And I almost became a biology major and have the highly nerdy distinction of being the only person I know who enjoyed studying for the MCAT.
How interesting. I’ve always wondered why that was. You learn something new everyday.
Off topic, but – You enjoyed studying for the MCAT? I didn’t know you were supposed to study for it. I wouldn’t even know how to start studying. I didn’t know of anyone who studied. I googled and discovered that they have MCAT prep courses now. I don’t think anything like that existed in my student days.
I’m new to this blog and am not a scientist. Many of you have commented about Robb’s post, but I thought I could add one thing to this discussion,
rob says “In cases of say, treating cancer, it would be crazy to rely on historical use alone, but in other examples, say you’re experiencing indigestion with gas, bloating, cramping – you’ve read that peppermint and fennel have long been used for that, there’s some small studies reinforcing the historical use, there’s a plausible mechanism of action, it’s not a life threatening condition, etc. In a case like that, why would I wait for an RCT to tell me whether I should try it or not?”
The constellation of symptoms: bloating, urinary frequency, feeling full after eating, and pain, are more likely to occur in women with ovarian cancer than in the general population. http://www.wcn.org/articles/types_of_cancer/ovarian/symptoms/concensus_statement.html
It seems to me that treating bloating with peppermint could easily delay cancer diagnoses.
gears,
Difference between salicin in willow bark and ASA is that you don’t get the antiplatelet and stomach irritant effects from it – it’s still useful for pain and fever but not for any cardiovascular benefits. On the flip side, it doesn’t lead to gastro-intestinal bleeding. I’m sure you’re not serious about the chewing on willow bark remark, extracts standardized for salicin are available.
Yes, CBD and THC is the synergy example I was referring to – these are just two compounds amongst hundreds. My point was simply that single molecule standardized drugs are not always inherently superior. Marijuana is one example. St. John’s Wort is another. It was long thought that hypericin was the main active ingredient. Later it was found that other constituents (hyperforin and various flavonoids) also contributed to its overall effects and were beneficial to be included in the extract. Reductionist theories are almost strangely ideological sometimes. Why is it so difficult to understand that compounds naturally found in the same plant modulate the effects of each other, sometimes in advantageous ways that single molecule drugs can’t replicate? I’m actually all for standardizing them if naturally occurring amounts are not sufficient, but the idea that there is only one possible active ingredient in a plant and that it should always be made into a drug just isn’t true in all cases.
I think we’re coming from very different places on the isolation/standardization topic. Your examples of standardization and isolation improving safety I’d agree with because they deal with compounds that are potentially toxic and involve more life threatening conditions and uses but generally safety is not the issue in most cases with herbs, efficacy would be the reason to standardize, and then often for multiple components. In some cases, simple water extraction (aka tea) or alchohol extraction without any standardization (aka tinctures) is enough to deliver benefits.
@Robb,
“you don’t get the antiplatelet and stomach irritant effects from it”
Other sources disagree with you. For instance:
This study showed that salicin affects platelet aggregation, although to a lesser extent than aspirin: http://www.ncbi.nlm.nih.gov/pubmed/11345689?dopt=Abstract
“Side effects tend to be mild. However, stomach upset, ulcers and stomach bleeding are potential side effects of all compounds containing salicylates. Overdoses of willow bark may cause skin rash, stomach inflammation/irritation, nausea, vomiting, kidney inflammation, and tinnitus (ringing in the ears).”
http://www.umm.edu/altmed/articles/willow-bark-000281.htm#ixzz27iQnnXL
GI bleeding induced by salicin was suspected of killing a dog http://www.ncbi.nlm.nih.gov/pubmed/15526604
And salicin was suspected of killing Beethoven. http://www.webmd.com/vitamins-supplements/ingredientmono-955-WILLOW%20BARK.aspx?activeIngredientId=955&activeIngredientName=WILLOW%20BARK
And as for comparing single molecule standardized drugs to herbal products, you can’t go by generalizations: each case needs to be tested individually.
Heh. I always have read that the reason we medicinized willow back is that it made the “aspirin” more tolerable, and decreased the GI and other side effects. To suggest that we would be better off chewing bark instead of taking precision doses is ridiculous.
Thanks! Had one. I figured you would recognize the difficulty of the synthesis (of course, nothing even remotely difficult by your current standards, but not bad for an undergrad, eh?)
Well, I actually did not study either. I took a few practice exams about a week before I took the real thing. And I managed a 38.
-Dr. Hall- The test has changed since the time you took it. I understand from my step-father (who is a critical care pulmonologist and graduated med in 1974) that back then it was much less involved and much more “general knowledge” than it is these days.
A 38 and you went to an Australian med school? *cough* bs *cough*
When I took the MCATs they were scored like SATs, so I wouldn’t know what 38 means.
@robb:
Since you are such an expert, perhaps you would like to describe to us the mechanism of aspirin causing stomach irritation and GI bleeds? And perhaps differentiate that from salacin? You know, since you clearly know so much about exactly why herbals are better than pharmaceuticals, the mechanisms of actions to actually explain why should come quite easily, no?
It’s not. And in fact, nobody here would disagree in principle. Merely in degree and in application. First off, most plants wouldn’t exhibit bioactive synergy and if they did it would be a negative syngergy. I mean seriously, think about it. Why – really why?? – would evolution create a selective pressure for a plant to become better and better at helping heal us? (I.e. be consumed by us?)
But in any event, the history of the topic has shown us that, to date, the vast majority of ancillary compounds are not particularly helpful. That said, we do use synergy to our advantage in medicine. My board exams had questions which basically consisted of “Patient has [X] and is currently on drug [Y] and has [Z] lifestyle and was diagnosed with [A] – what drug should you give?” with the intent to be identification of a drug that would act in synergy with the drugs he is already on and minimizes the side effects that would most affect his life. The converse is also true – patients on multiple drugs need to be managed to be sure that synergy doesn’t make one drug act too much or too little.
Of course not. Straw man. But research on ancillary synergistic compounds is insanely complex. It is ongoing. In fact my own post-grad research was in – come on take a guess? – no? Herbal compounds. I designed and ran assays to test Rhodiola rosea as an anti-aging compound. With the purpose of finding all the compounds that worked to create the effect. But lets break it down here.
1 compound to test for efficacy = 1 large complex trial.
2 compounds to test for efficacy =2 large complex trials.
2 compounds to test for synergy = a THIRD large complex trial
3 compounds to test for synergy = SIX large complex trials
4 compounds to test for synergy = 24 large complex trials*
See how that gets out of hand quickly?
The point being… well… lets get to another point of yours:
What does that mean? There is no ideology about saying that if you want to claim synergy between multiple compounds that the only way to verify that is to test the combinations. Nobody doubts that synergy exists. Or that herbal extracts can exhibit it. But you can’t just claim it exists for a specific combination for a specific indication willy nilly. You have to TEST it. And, as we all learned (wait, maybe it was just me?), in elementary school the more variables you add the more impossible it to test a claim. So “reductionism” as this obvious pejorative you use is indeed the only way to actually know the answer. If you just claim that 20 compounds act synergistically for a specific condition, you could run a trial. Lets say, for argument’s sake that the trial shows it absolutely works. The condition is unequivocally improved. Not even evil ol’ reductionist me would argue with you.
Prove to me that all 20 compounds are necessary for the outcome. Prove to me that it isn’t that 10 of those compounds are actively synergistic, 5 do absolutely nothing, and 5 are just mildly harmful, adding to a total positive effect. Or prove to me that only 1 is the actual active compound, 18 do nothing, and one has really nasty side effects in just some people. And then prove to me which of the 19 compounds has that really nasty side effect in just some people. Oh, and then prove to me that the side effect is only from the single compound and not a synergistic effect from 2 (or more!!) of the remaining 19 compounds.
Do you see the issue with it? 20 compounds have a possible 2,432,902,008,176,640,000 combinations to test. Heck, only 5 compounds need 120 trials to evaluate it.
So no, Robb. It is not that we deny synergy exists. It is that we have very good reasons to a priori assume that it isn’t automatically tailored for us by all the random plants out there AND that to actually test out possible synergistic relationships is worthwile but takes a lot more time and information than we have. The crux is that to then simply assume that a particular set of compounds is synergistic and the most effective without unwanted side effects is ludicrous.
So nothing ideological here. It is merely the rigorous application of tried and true, basic scientific principles.
@SH:
It’s a fact. I can certainly appreciate your… skepticism. But if you like I can try and dig up my score and send it your way.
Sure, send it to nobodyscoresa38andgoestoaforeignmedicalschool@bctheywillforeverhavetojustifywhytheywentinanothercountryinsteadofarespectablestateschool.com
well said mho. I am heartened that a non-scientist can apply some basic critical thinking and come up with a very sensible view on the topic.
wow SH. Honestly, have I ever given you any reason to think I would flat out lie about something? Or to be a flat out dick towards me? I did score a 38. And yeah, I did have trouble getting into a US school. And I could just leave it at that, and move on. But just because you seem to willy nilly enjoy being a dick to absolutely anyone for any reason…
If you think that an MCAT score alone can get you into medical school than you are a f*&#ing moron. But go right ahead and make assumptions all you want. Keep using that amazing skepticism of yours to ignore other possibilities.
This seemed appropriate in general:
http://sphotos-b.xx.fbcdn.net/hphotos-prn1/603788_478576012163415_1236686373_n.jpg
Holy crap. An MCAT debate? I almost went to bed. I studied hard for it, and I did not enjoy it.
If anyone cares, I was on a med school admission committee about 7 years ago. Back then a 38 was about 4 standard deviations above the mean (mean about 26, SD about 3). So a 38 is excellent. Now, please don’t waste your brain power in dermatology.
Indeed. I was just having a nerd-bro moment with gears. I hate to say it, but SH’s comment did get to me a bit. I have no reason to lie, or exaggerate, nor would I.
As for me, I plan on IM followed to CC pulm. My Step 1 was a 242. Not as good as I’d hoped, but good enough. What are your thoughts skeptical? Is that number believable? I know, it is only about 2 SD’s above the mean so maybe that one actually is legit. Right?
I mean seriously, you are a smart guy and you know your s$!t. But you really actually are an a$$shole. What was it that burned you so bad? I remember being a smoldering pile of angst and anger. It really isn’t worth it.
I remember in the ER where I worked for 3 years before I started med school that it was oft said one should prefer an a$$hole doc who knows his s$!t than a really nice guy who is a moron.
How about a really nice guy who knows his s$!t?
“I mean seriously, you are a smart guy and you know your s$!t. But you really actually are an a$$shole.”
A two finger or three?
Feh. Bring on the old GRE scores.
Why do you keep calling me dollar signs?
Eh, probably a two. I’ve met worse.
“I remember in the ER where I worked for 3 years before I started med school that it was oft said one should prefer an a$$hole doc who knows his s$!t than a really nice guy who is a moron.”
This always cracks me up. I have never heard this comparison in any other field.
It’s like saying…
Would you rather be pulled over by a cop with PTSD who’s on steroids or a corrupt cop?
Would you rather have a blind pilot fly your plane or one with a panic disorder?
Would you rather have a hairstylist with advanced hand tremors or one with no sense of style?
Would you rather the driver next to you on the freeway be drunk or nightblind?
Really? I mean, I can see social incompetence being tolerated when a doctor is primarily working on unconscious people, but in a doctor who needs to communicate with patients to reach a diagnoses and communicate a treatment plan it seems that NOT being an assh0le should be considered a core competency requirement.
This really must be a medical culture thing. In my experience with tech companies and military/automotive engineering, brilliant assh0les are rare…much more common are assh0les who think they are brilliant. Often behind that sh1tty personality is incompetence. And I don’t mean smart but hard to work with incompetence, I mean running your company into bankruptcy with bad decisions incompetence AND ignoring fuel system safety design flaws in school buses incompetence.
But thanks for calling SH on his attitude. I would add that his remarks to you are only complemented by his trolling on the CFS post.
Love a good SH rant.
“Would you rather have a blind pilot fly your plane or one with a panic disorder?”
Not a good comparison. Imagine you are getting on a plane to Japan. Which would you rather hear from the flight attendant?
1. The pilot is a jerk, but he is the best.
2. The pilot is such a nice guy, but he is the worst pilot I have seen.
That is the idea. Probably more applicable to a procedure based specialty. In reality, good people skills and communication are also very important. Doctors without them usually don’t have successful practices.
And there definitely are incompetent a-hole docs.
It always amuses me when people call out corporations for having a system that allows them to make a profit, then offers up herbal medicine as an alternative. Do all herbal doctors do this as a hobby? Because otherwise that’s quite the hypocritical double-standard for criticizing corporations for making a profit while ignoring practitioners of herbal medicine for doing the same thing. People practicing herbal medicine have just as much an invested interest and financial motive in their paradigm and approach as companies, but havea a far, far, far smaller evidence base. Corporations are generally really good at doing at least one thing – making money. Ideally that comes by selling a large amount of products people want for a low price – but not always. They’re also often good at developing new things to sell, including medicine. And many corporations do ethically, legally and morally dubious things while doing so. But please – show me a perfect solution, don’t pretend they’re unique for wanting to make a profit. And if it pisses you off that much, perhaps you might want to start some sort of campaign finance reform activism. A hell of a lot more fruitful than being a hypocrite on the internet.
jmb58 – I’ll tell you what, how about?
1. The pilot is such a nice guy, but he is the worst pilot I have seen.
2. The pilot is a jerk who bickers with air traffic controllers, discounts flight attendant’s reports of suspicious activity and antagonizes his co-pilots.*
Is the second really acceptable, because the first is worse?
Also you said – ” In reality, good people skills and communication are also very important. Doctors without them usually don’t have successful practices.”
I really hope this is generally true, but my assh0le reproductive endocrinologist seemed to do quite well by being the only RE available through the local HMO. So? Ultimately, I’m grateful, because it was partly his poor communication skills that helped us to decide against IVF and for adoption, so it worked out in the end, for us.
*Actually, my brother was a commercial pilot and, yup, he’s kinda a dick, but he got along very well with his crew and generally his passengers…because he was good at his job and that was part of his job.
Oh whoops, editing error.
“2. The pilot is a jerk who bickers with air traffic controllers, discounts flight attendant’s reports of suspicious activity and antagonizes his co-pilots.*
Should have read “2. He is a technically excellent pilot who bickers, etc”
you get the drift.
nybgrus,
I’ll ignore your patronizing condescension (while you are simultaneously being offended at the way someone else is commenting on you) to respond to some of your comments and questions because you do at least ask good ones. Please show me where I have once ever called myself “an expert”. It’s such a stupid term – there’s always more to learn and know. Anyway…
ASA came about as a response to pure SA being too harsh and causing bleeding side effects. ASA is still more likely to cause GI irritation than salicin though. Salicin is like time release SA due to it needing to be metabolized – making it less effective for acute pain but longer lasting.
Steinegger E. et al. Analytic and biologic studies on Salicaeae substances. Pharmaceutica Acta Helvetiae 1972; 47:222-234.
As far as its mechanism of action with the byproduct of GI bleeds, I’m sure you know this already – and anyone can look up Aspirin on Wikipedia to read about it inhibiting COX-1 and 2.
Most of your synergy comments I totally agree with. People were denying it exists though, which is why I was going into more detail about it. The reductionist ideology comment came about from people saying that single isolated compounds are always better. Maybe that wasn’t you. I agree with Harriet as well that generalizations aren’t any good here. Each plant and each synergy would have to be assessed separately. I’m sure there are all kinds of exceptions ranging from 1 isolated, standardized compound works best to multiple standardized compounds to *gasp* the full spectrum of compounds in the whole plant. As such, I retract my comment about standardization and isolation generally leading to more toxicity or side effects – it was an ill thought out generalization that has some examples (salicin vs. ASA and Marinol vs whole cannabis as far as degree of side effects) but probably isn’t true overall.
I’ve also never said synergy should be a priori anything. I’ve said examples exist – I believe it to be relatively common amongst medicinal plants – but of course it needs to be researched before assuming anything and just to learn exactly how it works. Synergy is just an effect that can be good or bad – the specifics are everything. That’s cool that you have been researching Rhodiola – last I’ve read salidrosides and rosavin were the main actives standardized for but I’m not sure if there’s any more recent that have been discovered to also contribute to the overall effects.
@Robb,
“exceptions ranging from 1 isolated, standardized compound works best to multiple standardized compounds to *gasp* the full spectrum of compounds in the whole plant.”
It seems improbable to me that any effect could require “all” the compounds in a plant. Can you cite any examples?
Harriet,
Sorry, I should clarify – I didn’t mean to imply that there are cases where “all” the compounds (hundreds or thousands in some cases) were necessary for the effect – more that the whole plant has a large number of known active ingredients and that the whole plant is sufficient to produce beneficial effects, making standardization unnecessary. By whole plant, I am not referring to eating leaves or anything that silly – but to full spectrum aqueous-alcoholic extracts. I won’t rely on the marijuana example as I’ve used it already and it isn’t even an aqueous-alcoholic extract typically. So – another example would be artichoke leaf for IBS symptoms: http://www.ncbi.nlm.nih.gov/pubmed/22363129
Still, having said that, if there are a number of known active ingredients, manufacturers still generally test for these and select raw materials based on them being present in sufficient amounts. There’s of course a range that they would naturally occur in but it generally doesn’t fluctuate that dramatically. To use an analogy, when you eat an orange, you’re going to get a range of vitamin C, and as long as it is grown and harvested correctly, you can count on that range to be consistent. Depending on what the vitamin C in the orange is being taken for, maybe an orange is enough (preventing deficiency), or maybe you need to concentrate it more (a whole fruit extract) or maybe you need precise large amounts that research has shown work best (a standardized extract). The artichoke leaf example above is the 2nd category.
@Robb,
“more that the whole plant has a large number of known active ingredients and that the whole plant is sufficient to produce beneficial effects, making standardization unnecessary.”
I’m not sure I follow your reasoning that “makes standardization unnecessary.”
And I’m concerned that along with the known active ingredients there might be a lot of unknown and/or untested ingredients that don’t add anything to the effect and that might even counteract the desired effect or cause adverse effects.
Harriet,
Using the artichoke leaf example, it has been shown to be of benefit for IBS symptoms and hypercholesterolemia without the need to standardize specific ingredients because known active ingredients already come through in sufficient amounts with a simple aqueous-alcoholic extract. I guess you could say that this means the simple extraction process already provides some degree of standardization though. As far as unknown/untested ingredients that could cause adverse effects or counteract the effects, this is possible in some cases but not for artichoke leaf, as it has already been shown to be effective. Maybe standardizing further would produce even better results. Cost vs. gains in effectiveness becomes a factor at some point though.
@robb:
Completely different. One is a case of me making a claim about myself on a forum where I have established credibility over the last 3.5 years of regular commenting as a consistent and honest person. The other is you making claims about evidence and the herbal compounds that are either entirely wrong and based in fallacies or partially wrong by over extrapolating the paucity of data on a topic to reach conclusions with significant confidence that is wholly unwarranted (i.e. coming off as an expert).
I can’t seem to find a copy of the article you referenced to actually read. It is funny how you retract your statement about “standardization and isolation generally leading to more toxicity or side effects ” and once again cite “salicin vs. ASA and Marinol vs whole cannabis as far as degree of side effects” as the basis for your concededly incorrect over generalization, yet in your opening paragraph say “ASA came about as a response to pure SA being too harsh and causing bleeding side effects” while then asserting that salacin is still less likely to cause GI irritation. This is without cited without evidence and taken at face value belies a lack of critical though on the matter. Perhaps ASA is more likely to give you irritation but if it is less likely to make you bleed then the side effect profile has improved. Which is exactly my thesis and contradicts your own.
Bollocks. Nobody here denied it and no doctor could possibly deny it. It is a basic and fundamental principle of pharmacology. One we use to our advantage when combining antibiotics (the old and classic example is trimethoprim and sulfamethoxazole) and the other we watch out for when combining drugs. You were fighting a straw man that whole time. And nobody here has made the claim that ” The reductionist ideology comment came about from people saying that single isolated compounds are always better. ” Your discussion on the topic lacked necessary nuance and paints the views here as all or nothing quite erroneously.
What we do question is your assertion that “multiple standardized compounds to *gasp* the full spectrum of compounds in the whole plant” would be at all beyond infinitesimally unlikely to be better than fewer compounds. We further questions your assertion that ” I’ve said examples exist – I believe it to be relatively common amongst medicinal plants”
For the second statement, that is quite simply and absolutely evidence free statement. There is literally nothing to support your claim that it is “common” no matter how you wish to define the word. And in fact there is heaps of evidence to demonstrate that it is quite uncommon. The fine line there is that it is indeed possible to create a synthetic drug from a plant extract which has a significantly higher side effect profile than the plant itself. Which would provide a very narrow example of the extract being “better” but certainly not best. And as we have seen, as rigorous trials of herbals are done we find the effect size to be smaller and smaller to the point of clinical insignificance. Saw Palmetto being a prime example – as the data piled up and more robust studies were done we find it has no effect beyond placebo.
Which leads me to your first assertion. I would argue that a whole plant extract could never be better than isolates of single or just a few compounds from it. As I pointed out it makes no sense for a plant to have evolved to perfectly suit our medicinal needs. Thus, a whole plant extract will inevitably contain many completely neutral and some actively harmful compounds in varying quantities. Furthermore, biology is extremely – extremely – complex. Taking a system as complex as the human body and throwing in just ONE compound to try and achieve a positive effect is phenominally difficult and due to our current neonatal level understanding of proteomics and genomics, cannot possibly be extrapolated individually with any sort of reliability. Throwing in multiple compounds at a time, with bioactive properties we haven’t even begun to study is simply ridiculous. Claiming further that doing so is a priori better (which is exactly what you are doing since you have zero evidence to back your claim) is utterly inane.
And that is really the point. There is zero evidence to demonstrate whole-plant synergy is useful. There is plenty of evidence to consistently demonstrate the inferiority of herbal extracts (often to the point of nil efficacy). There is a priori reason to assume that a plant would not have evolved to suit our medicinal needs. And there is every basic logical reason to know that mixing in a plethora of unkown compounds to a therapy will, on the whole, be vastly more likely to have at least a small deleterious effect than any positive one. You even realize this yourself:
Yes, bad. And more likely to be bad. Which is why one cannot be truly educated on the topic and apply critical thinking and still claim that whole plant extracts are useful to be prescribed as therapy. The only exception is if efficacy has actually been shown, side effects have been demonstrated minimal, and the active molecule(s) has yet to be identified – all from the same kind of trial data that a regular drug would have to go through. Even then, it would still make sense to reduce down to the bare minimum of active compound(s) and purify them (and, as has often been shown, modify them to reduce side effect profiles and increase efficacy and improve pharmacodynamics).
As for my Rhodiola work, that was many years ago. And it was (and still is) extremely promising. But my PI makes it a point to say that this is still very preliminary, we should not be prescribing it to everyone, and that we need to further isolate the active compounds while attempting to look for beneficial synergy.
You are missing the point. Celebrex was pulled off the shelves because of an effect so small it took after market surveillance to notice it. The issue at hand is not if the extract can actually extract enough of the stuff that helps IBS. It is whether it can extract TOO MUCH as well as extracting all the other stuff that may be harmful in such a small efffect size that Phase II or III trials can’t pick it up. But if it does have an effect (which would be extremely hard to measure and find under the DSHEA) the whole thing would have to be pulled since it would be impossible to tell WHAT was actually causing the problem. And, as I explained above, the chances that out of 100′s or 1000′s of compounds in a whole herb extract that at least 1 or 2 would cause such harm is essentially gauranteed.
Standardizing further will ALWAYS produce better results. Because then we can know about precise dose response curves and actually have specific compounds to hunt down for signals. Pick up some $hit, throwing it against a wall, and hoping something sticks is not a good way to go about medicine.
@nybgrus
SH comments didn’t seem offensive to me until I started reading your objections. I just thought he was surprised you couldn’t get into an American school with such a great score. I didn’t see anything insulting. Your interpretation was that he didn’t believe your score, but I didn’t see that at all and was startled by your reaction. Now I’m just confused.
@SkepticalHealth
See the above about your first entry to nybgus. Which was it?
As to the second: Why should nybgrus be embarrassed about going to med school in Australia–or anywhere else? At least they are civilized enough to have a national health care system. I cannot imaging thinking a doctor I might see who went to an Australian medical school would be suspect in any way based on that alone. Nor can I imagine asking him why he was “dumb” enough to do so. I’ve had fabulous docs that went to med school all sorts of places–Canada, India, Philippines. Many did their residencies here and work at prestigious hospitals that I presume checked them out to some degree.
Where did you go? Do tell.
nybgrus,
I think the discussion value is probably on the wane here – or at least I’m losing interest in responding to all your points but as far as your last post, how can you equate Celebrex (a novel compound) with artichoke leaf (in our food supply for ages) as an example where “there may be harmful stuff” that small trials haven’t picked up yet? Have you looked at the statistics on deaths due to pharmaceuticals vs. those of herbs? While herbs being used since antiquity isn’t a reason to say they must be effective, it does help a lot in terms of safety. It’s a long time and throughout large populations for potentially dangerous ingredients to make themselves well known. I can assure you there are no secretly malicious ingredients in artichoke leaf waiting to be sprung on an unsuspecting public.
So please explain how you came to the conclusion that “out of 100s or 1000′s of compounds in a whole herb extract that at least 1 or 2 would cause such harm (not sure what degree of harm you mean here) is essentially guaranteed.” That’s a strong statement. That’s a strong generalization. Surely you must have something concrete to back that up. Are you talking about 100% of herbs? 90%? What is this based on?
Most dangerous compounds in commonly used herbs are well known by now. Take butterbur (Petasites hybridus). It contains pyrrolizidine alkaloids, concentrated in the root. Not good stuff for your liver. So extracts (clinically proven for migraines) are made using a process (super critical CO2 extraction) that ensures they don’t come along for the ride. Or strains are cultivated (the Vienna strain) that don’t contain these alkaloids. Who makes the decision that certain herbs can be grandfathered this way and certain ones are rarer and less well-known and should not be assumed as safe? That’s what the FDA, or Health Canada, or the TGA in Australia, or whatever the government authority is there for. And they completely disagree with you as far as the commonality of dangerous compounds in herbs.
Janet,
“Why should nybgrus be embarrassed about going to med school in Australia”
That was my first thought. Our med schools have produced doctors who have discovered the true cause of stomach ulcers, and the first vaccine against the HPV. Is there any evidence that med schools in the USA are superior? And, yes there is our universal health care system which functions twice a well for half the cost and covers everyone without exception as well as a private healthcare system that cannot discriminate on the basis of a persons state of health.
But SH definitely did not believe nybgrus score on the basis that he he attended an Australian medical school. I think that’s pretty clear.
Celebrex was pulled off the shelves?
I think you mean Vioxx.
@Janet, @BJ,
@Nybgrus is an American. No American that can get into an American medical school voluntarily goes out of country for medical school and then comes back, because it is fraught with difficulties. He will forever be classified as a foreign medical grad, and one always has to wonder why that person had to go to a whole other country just to attend medical school.
The score that he claims to have made is higher than the average for admission to Harvard Med. Money for admissions is not an issue, because any and everybody can get student loans to pay for medical school. And I’m sure we all can tell, for as self-important and narcissistic nybgrus is (ie, as a third/fourth year med student, he acts like he’s actually doing neurosurgery, or that his decisions or notes (in charts) actually matter. Etc. He isn’t, and they don’t!), we can be damn sured if he was able to get into a remotely respectable medical school, he would, and with a score like that, he’d be welcomed into the best of the best.
And regarding Australian schools: generally in America if you can’t get into an American medical school, you apply out of country, and common out of country places are Australia, Mexico, and the Caribbean. Some actually goto Poland as I understand, but I’m not really sure. Everybody has a reason to go there, and the vast majority of reasons are that their MCATs or grades were low, or perhaps they have a criminal record, but that would probably lead to licensing issues later down the road.
So, for nybgrus to end up in Australia, instead of a prestigious school in America with his claimed score, he either has a huge black spot somewhere on his record, something so bad that he had to go to a whole other country for, or he lied about his MCAT score. I’ll take the simple solution and go with “liar.” Give my regards to the ECFMG.
@Janet, where did I go? A non-prestigious state school. My MCAT score? Unimpressive.
@janet:
from SH:
So yes, clearly stating not only disbelief, but a clear pejorative of the Aussie school system, stating that a “respectable state school” would have been a better option. Even though in the latest worldwide ranking my institution ranked 33rd in life sciences and medicine in the world last year and 90th in medical schools specifically worldwide this year (which places it higher than Boston University, Texas A&M, Washington U in St. Louis, UC Irvine, Davis, Riverside, Santa Cruz, Dartmouth, Brown, Baylor, Mayo, Tufts, Purdue, Rice, Michigan State, Case Western Reserve, Colorado State, Iowa State…. need I go on?). And my clinical training is at an institution ranked in the top 5% of academic teaching hospitals in the US, with 3 NIH R01 grants, and ranked in the top 100 hospitals in the US for Stroke, GI, Critical Care, and Pulmonary Care….
So which respectable state school did you go to SH?
@BJ: yes, I meant Vioxx.
I realized my comment I wrote just as SH was writing yet another @sshole comment is because one of my quotes of him came out as a link making three. Here it is fixed:
@janet:
from SH:
A 38 and you went to an Australian med school? *cough* bs *cough*
Sure, send it to nobodyscoresa 38andgoestoaforeignmedicalschool @ bctheywillforeverhavetojustifywhytheywentinanothercountry insteadofarespectablestateschool.com
So yes, clearly stating not only disbelief, but a clear pejorative of the Aussie school system, stating that a “respectable state school” would have been a better option. Even though in the latest worldwide ranking my institution ranked 33rd in life sciences and medicine in the world last year and 90th in medical schools specifically worldwide this year (which places it higher than Boston University, Texas A&M, Washington U in St. Louis, UC Irvine, Davis, Riverside, Santa Cruz, Dartmouth, Brown, Baylor, Mayo, Tufts, Purdue, Rice, Michigan State, Case Western Reserve, Colorado State, Iowa State…. need I go on?). And my clinical training is at an institution ranked in the top 5% of academic teaching hospitals in the US, with 3 NIH R01 grants, and ranked in the top 100 hospitals in the US for Stroke, GI, Critical Care, and Pulmonary Care….
So which respectable state school did you go to SH?
Argh. HTML tags: Sorry, link for references above:
http://www.shanghairanking.com/ARWU2012.html
http://www.topuniversities.com/university-rankings/world-university-rankings/2011/subject-rankings/life-science-biomedicine/medicine?page=1
And as for the rest of your wonderful screed… no, I am not doing neurosurgery. And yes, I am well aware of my role and my place in the hospital. But I do manage my own patients, I have dictated their care, I see them entirely on my own and present to the attending, and my notes and orders do go in the chart countersigned by the attending/resident and make the medical record of the patient. I have come up with assessments and plans – which were implemented for patients – I have caught lab values and physical findings that the residents missed, and I even caught a vertebral crush fracture that the radiologist missed the read on. My institution expects me to be part of the team and gives me independence as I show competence. And every single review I have had for my rotations has been excellent, with most stating outright that they feel I work at the level of an intern.
So rather than think that I am lying about my score – which yes, I am well aware is higher than Harvard’s average admissions MCAT – why don’t you consider that I am going to a vastly better medical school than you did, am getting a better education, and get your US-centric head out of your @ss for a change? I get the feeling if you were my attending you would be the only one I would write up for being a dick. And where I am training, that is a very big no-no.
Bah. Piss off. I can’t believe I even had this conversation with you. Thankfully I know when I am an attending they will have a doctor who is smart and nice, which is way more than can be said for you.
Haha! I still haven’t seen your justification for going to a whole other country for medical school. Why don’t you just admit that you lied?
They’ll also have an attending that’s completely full of crap
I have to admit, it’s funny seeing you so upset – all because I called you out on your pitiful MCAT lie. It makes me wonder, how much do you hate yourself if you have to lie about your credentials? (Well, you really don’t have credentials, you haven’t even finished school yet.)
@robb:
Because the principle is the same. Small effects are hard to pick up, no matter where they come from.
Show me actual robust statistics for the deaths due to herbs. They don’t exist. Because there is not even remotely the same level of monitoring.
No, it doesn’t. Aristolochia fangchi was used in Chinese herbal medicine for a very, very long time before the very large effect of nephrotoxicity was noticed. Licorice leads to hypokalemia, hypertension, arrythmia, and edema. The list goes on. Blood letting was thought to be efficacious when in fact we know it lead to increased mortality and morbidity. The point is you simply cannot assume that something is safe because it has been used for a long time. It needs to actually be studied specifically for that – even for large effects like Aristolochia fangchi but especially for subtle effects.
Really? How? You have absolutely ZERO evidence to back up that statement. Extracting the contents and ingesting it in larger quantities than would otherwise be normal has not actually been tested. And, as I pointed out above, it could actually have that effect in smaller quantities that we simply have no way of actually detecting since the effect size is so small.
It is based on the fact that the corpus of scientific investigation has demonstrated that any given compound is more likely to do harm than good. It is MOST likely to do nothing. And yes, I mean any degree of harm – not just death or overt illness. And I am talking about 100% of anything we ingest or inhale in any way. There is simply more likelihood of harm than good. Most of the time that is absolutely minimal and/or unavoidable. And there is the interesting question of hormesis that could come into play. But in general, when you have zero evidence to demonstrate actual efficacy of something for an indication, giving it along with a slew of other compounds is playing with odds that are not in your favor.
That is just purely asinine. We don’t even KNOW what most compounds in commonly used herbs ARE, let alone if they are safe or not. And as I said about Aristolochia fangchi, a POTENT nephrotoxin was completely missed until 2005ish. Let alone the more subtly toxic substances.
And then you go on to further demonstrate how purification and reduction of ancillary compounds is better… which is exactly what we have been saying here and exactly what you have been arguing against.
Nope. Those are covered by the DSHEA in the US and respectively similar laws in Canada and Oz. The regulations are shockingly lax as has been repeatedly discussed in great detail at this very blog. I suggest you educate yourself on the topic before you continue making evidence free assertions.
I didn’t lie. I have no reason to lie.
And the program I am in is only available to US citizens and is better than any program I could have gotten into here in the US. Additionally I hold more than just a US citizenship. My fiance completed her masters in hypersonics engineering at the same Australian institution (which is #1 in the world for her type of research). And once again, if you think that merely an MCAT score can get you into school and that ONLY a HUGE black mark would prevent that with a 38, then you truly are an idiot and have no idea what you are talking about.
As for my attendings… I have actually changed the course of management of patients because of my own assessment. I defended myself and the attending agreed and opted for my course of management. So seriously, piss off. Be a dick as much as you want – you only look like a fool for it. But for chrissake why on earth assume I would sit around and lie about anything, let alone that? Give me some time… I can’t log in to my Thx but have sent an email for my score. I am happy to settle it.
Did you happen to notice the university at the top of the first list you posted? Yeah, you’re supposed score would have got in you in there. … I’m going to teach you a good life lesson. If you are going to tell a lie, at least make it believable. You could have gotten away with lying about a 31 or something, but you had to go and just be ridiculous about it.
So, what’s your black mark that made you have to go to a sub-standard program in another country?
For the record, I don’t care what any commenter’s MCAT scores were or what school he went to. All that matters to me is the content of the comments, and nybgrus’s have been consistently excellent. He is obviously intelligent and well informed and he backs his assertions up with citations. If he’s this good as a medical student, I’m predicting great things for him as a doctor and advocate for science-based medicine.
Also for the record: everyone please play nice. I’ve tried to set a good example, and I’ve asked before for commenters to abstain from personal insults.
You know why it pisses me off? Because I make mistakes. But I don’t lie. Call me out for being wrong on a topic, demonstrate my evidence is wrong, and I’ll thank you for it. But don’t call me a liar. Give it a few days to recover my password for Thx and we’ll see how you do when you eat your words.
Until then, you can piss off with your smug elitist asshole attitude.
I whole-heartedly agree. Even a-hole me has written that I think nybgrus is very intelligent. However, I absolutely don’t buy the MCAT story. I don’t think an American on planet earth would pass up Harvard Med, or any other prestigious medical school, to be a FMG.
Since SkepticalHealth keeps insisting: I have verified nybgrus’s MCAT score. It is 38. He was not lying. An abject apology is in order.
Ok, then nybgrus, what’s your black mark? Criminal record? Drug arrest? Kicked out of university for cheating? Because no person, in their right mind, would voluntarily go to a foreign medical school. You can’t justify that it any way as something you voluntarily chose to do, in lieu of getting an education at an American school, especially considering you dream about obtaining a critical care fellowship.
nybrgus – clearly we are going to need to see your birth certificate
SkepticalHealth,
You are out of line.
I have no idea what my MCAT scores were; I don’t even have any memory of being told my scores (1966 was a long time ago!). But I do remember the SAT. By analogy, you might accuse me of lying if I told you my SAT scores (800 and 776) and high school GPA (4.0, one of only 3 students with a perfect 4.0 out of nearly 800 in my class. You could say no one with those scores would have voluntarily gone to a mediocre public university when they were qualified to get into a prestigious Ivy League school. I happen to have had excellent personal and financial reasons for not even applying to any other school than the U. of Washington.
You can’t imagine why Nybgrus would have chosen as he did, but that might just mean that your imagination is inadequate.
You owe him an apology for falsely accusing him of lying. Is it so hard to admit you were wrong?
Instead of apologizing, you have stayed in attack mode and suggested he had a black mark like a criminal record.Now you owe him another apology for that.
It would have been so much nicer if you had started out by saying “With a high MCAT score like that, why did you choose an Australian school?” If you had asked nicely instead of attacking, you might have learned something beyond your poor ability to imagine.
In no way do I feel that I’m out of line. First of all, nobody asked nybgrus what his supposed MCAT score is. He volunteered that information, and he volunteered that information in a manner that implied he just winged the test and happened to get a great score on it. That’s one statement in a constant stream of narcisism from a medical student who obviously has some glaring, possibly career-stunting, blemishes in their record.
Second, just because Harriet says its so, doesn’t mean its so. I Googled “MCAT 38″ and found a dozen pictures of people screen capping their respectable MCAT scores. I have no idea what he supposedly sent you, but unless it’s his score, with his name showing, his photo ID with his name showing, and some sort of proof that “nybgrus” is whatever the real name is showing, then it’s absolutely meaningless.
But beyond that, I’m actually willing to believe he had a good score – I don’t doubt that he could do well. But it forces one to ask, why would he go to a foreign medical school? And that’s the question that I have not seen answered. There’s no good answer for it. Nobody on earth with a good record would goto a foreign school. You attempted to brag about your own accomplishments, but nobody really cares about a high school GPA, or even a college GPA. And you mentioned state vs. Ivy League – you’re right, there’s a comparison. However, either of them is infinitely more credible than a foreign medical grad. If I was looking for a partner or anything of the sort, I’d consider Podunk University of Idaho over anybody from Australia or any other foreign country. Furthermore, I’d bet good money than 9/10 residency program directors rank American grads ahead of foreign grads.
So yeah, Harriet, you can make whatever ridiculous post you want defending nybgrus, I don’t care, but it doesn’t change the fact that nobody with a clean record would pick a crappy foreign school, along with all the stigma that comes along with it, over an American Ivy League school. …. Seriously: what’s the justification? It certainly isn’t money. What, it was too cold up North? Be realistic. You don’t have an argument.
And, while obviously random internet user nybgrus doesn’t owe anybody an explanation of why he ended being forced into a crappy foreign medical school program, he at least could admit that it’s a fact that he has glaring issues that are forcing him to pursue substandard education that will blemish his record instead of pretending like he picked this foreign program on purpose, when infinitely better programs exist stateside.
Wow. Just wow.
Yeah, that’s what I thought about that completely ridiculous post you just made in the iron supplement thread. I can’t believe a MD is so out of touch with CVD!
“he ended being forced into a crappy foreign medical school program”
I see several assumptions here. Could it be he chose to go to a better school? What makes you think that other countries have substandard programs? You think the USA has the best programs in the world? Maybe it did at one time. Look around. Don’t you ever get the sneaky suspicion that we are a has been country? They even have a center for CAM at Harvard. BTW, I studied in Poland. Had a scholarship and finished school with zero debt. Of course, there are those who think they are superior because they studied here. But thinking doesn’t make it so. And I see that smug superiority less and less.
I’ve been reading this blog for a while and enjoy the range of comments and writing styles. nybgrus’s posts have consistently been among the most well-written, thoughtful and intelligent. While I always find out what medical school any of my doctors went to, I’m more interested in their residency (and fellowships, if any.) But above both is their commitment to the practice of medicine which in my opinion is at its foundation the willingness to be a good student, to always learn, to always have the open mind of science that allows a person to evaluate evidence and choose the best courses of treatment. As Dr. Hall noted and I agree, nybgrus’s future as a doctor seems quite bright and I think this is largely because he seems to be an excellent student.
And for what it’s worth, I hear that Australia is not only a very civilized place with electric lights, running water and fine beers on tap but also home to more than one excellent medical school that has bravely removed leeches from the laboratories and where the teachers even wash their hands.
I, too, want to come to the defense of nybgrus. Quill said essentially what I was going to, that I don’t think it matters where you went to school so long as you have a commitment to learning and critical thinking, and from lurking here for a while it’s quite clear to me that nybgrus is a decent, thoughtful person. That is what is important to me.
Furthermore, one of the points I hear repeatedly on this blog, by the editors and other contributors, is that medical schools (in the US, no less) do not equip their students with the critical thinking skills that allow them to easily dismiss pseudoscience and quackery. I was under the impression this was part of the push for formalizing “science-based medicine” and recognizing the place of prior probability in investigating therapies, because most people trained under evidence based medicine hesitate to say that homeopathy is the rank quackery that it is, for lack of insufficient clinical trials (and chiropractic and acupuncture and…). It seems to me that medical schools here in the US aren’t perfect, either.
Anyhow, I got your back, nybgrus. I’m glad you’re happy with school in Australia and best of luck to you. I don’t know why SkepticalHealth insists on being outright mean (SH: why’d you have to go and spoil our nerd-bro moment like that, man?). Just forget him.
Responding to things that happened a long time ago:
@HarrietHall:
I did study for the MCAT, and I think most people applying these days do study to a greater or lesser degree. I thought I was on the less insane end of the spectrum studying for a month and a half on my own and then taking practice tests like nybgrus, as opposed to the people who spend $2k on practice courses. People go a little crazy about it nowadays.
@Robb:
I guess the discussion is over for the most part, but I at least wanted to say that I don’t think it is that “ideological” or overly reductive to expect that, in the most likely case, there is one useful compound to be isolated from an herb. Biological activity is, for the most part, mediated by receptor interaction and the specific character of that interaction (right?). So I think it is reasonable to expect that one compound is going to have a receptor interaction that most effectively elicits the activity you want to produce, so you can leave everything else behind. And like nybgrus said, and what I think is most important to stress, that “everything else” is just as likely toxic as helpful. Even you cited an example where a supercritical CO2 extraction was required to exclude toxic compounds from an herb.
Also, the fact that you say we can’t compare Celebrex with artichoke leaf because Celebrex is a “novel compound” implies that you wholeheartedly accept the naturalistic fallacy, which is just not true. This has been debunked so thoroughly I won’t get into it, but come on, strychnine comes from an herb. And even though artichokes have been in our food supply for ages, it’s all about dose. Nutmeg has been in our food supply for ages, too, but if you eat a pile of that you hallucinate for like three days.
I didn’t realize I was going to set off such a firestorm with the MCAT comment. Sorry about that…
Oh, there’s no doubt that people can get a good education at foreign medical schools, but there is not a single advantage had by going to them, especially for someone who supposedly made a nice MCAT score. Even more so for a MCAT score that would get someone into an American Ivy League school. I can’t think of a single person who would rather a degree from Australia, Poland, or the Caribbean instead of Harvard Med. Even a program director would see this: “Would I rather tell people I matched Harvard grads, or foreign medical grads?” In America, there is indeed a stigma among people who went to foreign medical schools. It may be undeserved, but the stigma exists nonetheless. Furthermore, it makes the applicant less competitive for residency. The first question a program director is going to ask in an interview is “Why did you go to a foreign school?” He better have a good answer. I apologize if these facts are unsettling.
By the way, the anecdotes of “Oh, I don’t care where my doctor went to school…” are cute but irrelevant. We are talking about career climbing and getting into competitive specialties. When everything else matches up, the American grad is going to win over a foreign grad almost every time. After all, residency positions are paid for, in part, by American tax dollars. It’d be very screwed up if American students had to sit out because programs filled up with foreign medical grads.
First off, thanks to all for the kind words. Gears – it was a nice nerdy bro-moment. To more in the future.
Secondly, as a warning to any other potential med students out there, do not have the attitude about MCAT scores that SH has. A single score, no matter what, even in the context of decent undergrad GPA does not absolutely guarantee you a spot anywhere, let alone a top Ivy League. It was exactly that arrogance and brashness that led to me shooting myself in the foot during my first round of applications. Also, bear in mind the very significant importance of excellent letters of recomendation. It is one of the lessons learned the hard way I pass on to those asking my advice on the topic.
Beyond that, I feel little impetus to further explain myself except to say that as Dr. Hall pointed out, SH’s imagination is indeed extremely small and that I have absolutely zero concerns for my ability to match extremely well and achieve all the goals I have. Suffice it to say that my SoM has generated the highest USMLE scores ever achieved, has matched into places such as Dartmouth, has the support of state governments and my particular program has the official endorsement of the AAMC as an excellent up and coming program. Additionally, the dean of the UC San Francisco is a graduate of my SoM. I am not worried about explaining my choices. So indeed, assumptions make an ass out of you and me, but mostly you.
Once again, thank you to everyone else here for the kind words. Don’t feel it falls on deaf ears (err… blind eyes?) and I do genuinely appreciate it.
“there’s no doubt that people can get a good education at foreign medical schools, but there is not a single advantage had by going to them, especially for someone who supposedly made a nice MCAT score.”
While I accept this reasoning in general, I don’t think you can rule out any possible advantage. There might be factors that haven’t occurred to you or that would be personally compelling for a particular individual. I can think of a few possibilities: free room and board with a relative who lives near that foreign school, for instance.
I only applied to the one medical school I could afford to go to (because I could live at home). My pre-med advisor told me that with my GPA I would be guaranteed to be accepted if I were male, but as a female there was a strong possibility I wouldn’t be accepted and I should be prepared with a backup plan, like going into microbiology. I told her my backup plan would be to go to a medical school in Mexico that accepted all comers and was the next cheapest option. (My Spanish is fluent).
Why not give Nybgrus the benefit of the doubt and assume that someone as intelligent as he will have a good answer for the residency interview? Why assume he must be lying or a criminal? I still think you owe him an apology.
@SkepticalHealth,
“We are talking about career climbing and getting into competitive specialties”
Maybe some of us are. But some of us aren’t the competitive, climbing type. Some of us only wanted to get an adequate education so we could be useful treating patients and continue learning by keeping up with the literature. Prestigious medical schools may make it easier to get into prestigious residencies, but is that really what makes a good doctor? I don’t know of any evidence that patient outcomes are better when doctors have had more prestigious educations. Do you? I can think of at least one very ambitious doctor who went to Harvard Medical School and was highly motivated to climb the ladder to fame and fortune by spouting woo: Andrew Weil. From what I have seen of Nybgrus, I bet he would be a better doctor than Weil even if he went to one of the lowest-ranked medical schools. At least he understands science-based medicine and doesn’t advocate “stoned thinking.” That counts for more in my book than fancy credentials.
I have always enjoyed Nybgrus’s comments and could care less about his MCAT score.
I have been on a medical school admission committee and an admission comittee of a competitive surgical residency program.
A 38 will get the attention of most US med schools. Not a guarantied admission, but the attention. When people ask me advice about which med school to go to I tell them to figure out what is most important to them. If you want to go to a competitive residency, go to the highest ranked med school you can. That will increase your chances. If other factors are more important (lifestyle, money, family location, wheather, or whatever), you can get a great education in many different schools. For the most part med school is more about the dedication of the individual student.
As an exemple, my program has never accepted a foreign med grad or DO grad right out of school that I know of. Right or wrong, there is a bias. A number have joined after a preliminary internship and went on to be awesome surgeons.
That said, I’ll bet med school in Australia was a blast. I echo the sentiment that Nybgrus seems like he will be a great physician. Don’t overlook the surgical field. Trauma/critical care is a great place for evidence based medicine. Not so much surgical oncology. (kidding, Dr. Gorski)
@HH
Thankfully, I think medicine as a profession has come a long way in regards to sexism. The overall first year class has been >50% women for a while now.
@jmb58
“medicine as a profession has come a long way in regards to sexism”
It certainly has! My book “Women Aren’t Supposed to Fly” shows how far it has come just in my professional lifetime. When I graduated, only 7% of American doctors were women. And when I was promoted to Colonel there were only 13 women in all branches of the service who held a higher rank, and most of them were nurses. I like to think I played a part in changing things by serving as a good example of a competent woman in what was then a man’s world.
@HH
“I like to think I played a part in changing things by serving as a good example of a competent woman in what was then a man’s world.”
That is definitely something to be proud of.
I’ll check out your book.
Nybgrus,
Research has made substantial progress identifying the various constituents of many commonly used botanical supplements, including Rhodiola Rosea:
http://www.ncbi.nlm.nih.gov/pubmed/20378318
Artichoke Leaf Extract does have a history of safe use:
http://www.sciencedaily.com/releases/2008/07/080702170607.htm
The FDA is quite serious about monitoring adverse events for supplements. You can view the figures posted by the agency by searching the phrase, “Number of mandatory adverse event reports from the dietary supplement industry entered into CAERS”. Supplement manufacturers are required by law to report all serious adverse events related to their products.
Number of all supplement adverse events (serious and non-serious) for 2010 submitted to FDA: 830
Number of serious adverse events only for prescription drugs in 2010 submitted to FDA: 471,291
Dietary supplements, including botanicals, have a completely different level of risk compared to drugs. Supplements are inherently safe; prescription drugs are inherently unsafe.
@HH
Very true! I think ‘ol @nyb will be a fantastic critical care specialist one day too, if not a little long winded. We all have that one pulmonologist at the hospital, who knows everything, writes the admission protocols for the hospital, and is the one you can always bounce off of if you need a little advice. I’d say maybe nybgrus will be that guy one day, but I don’t want to bump his ego too much.
@jmb,
Are you an older or younger surgeon? I ask because I’m curious about the call schedule you went through. I’ve heard stories from older docs about insane call for surgeons, I believe I’ve heard Q2. I heard one story about this malignant surgical attending in Houston that would require his residents to essentially live at the hospital, and they got like one afternoon off a week, or something along those lines. I believe they now have 80 hour workweek limits, which I’m sure no program actually abides by.
@Dr. Hall: I can certainly say that prior to entering med school I was not interested in being a competitive climber. I can distinctly remember my sister trying to convince me to go for an MD/PhD and me saying “Why in the hell would I want to do that? An MD to practice medicine is PLENTY good enough!” Things have changed a bit since a bit before I started med and I have made sure my CV will make the FMG status a non-issue.
@jmb58: Thanks for the kind words. I actually had strongly been considering a surgical field but ultimately have decided against it. I like the OR but not that much. As for programs (such as yours) simply not accepting FMGs or DO’s, yes, I am well aware this exists. There are also programs that don’t accept from specific US medical schools and/or that do preferentially accept from specific US medical schools. I am well aware there are programs that simply will not look past FMG. However, many truly excellent programs do regularly accept FMGs and I did take all this into account when I made my specific decision. I had a few other options at the time and after speaking with many physicians, including a number who have sat on residency committees, I made the decision I did. To this day I have no regrets. A friend of mine went a different route and ended up at a lower tier US med school. In discussing our educations and opportunities for advancement and residency, it seems clear that I got the better end of the bargain on that one. Save for those programs which flat out have a policy against FMG and DO, my CV will look significantly more robust than his (well, except that now he has taken a leave of absence to do a year long regenerative opthalmology research fellowship funded by the NIH). Bear in mind (and this is not specifically directed at you) that there is indeed a difference applying as an FMG from the Carribbean vs and FMG from Oxford (not that I am at Oxford, but there *are* prestigious international programs). As I pointed out earlier, my SoM is ranked higher than many US SoM’s – even ones you wouldn’t think such as my undergrad alma mater, Brown, and Tufts. And I hold an EU citizenship in addition to my US citizenship (I was not born in the US) and that just added icing to the cake.
@Jeff: I am not going to bother deconstructing and explaining where your reasoning is just not quite right, since it has been done before and refuse to learn. Your last sentence is absolutely incorrect – something I demonstrated with Robb, so go back and read that conversation.
I should add that the reason my CV would look more robust is because of the opportunities afforded that I took advantage of. In other words, we felt that it was easier to take advantage of more opportunities at my SoM than his, though of course there is no limit in either one. Since he was interested in an academic career and recognized that many academic programs have that bias against FMGs it was in his interest to attend a US SoM of lower quality for exactly that reason. I was not interested in an academic track. I am a bit more interested these days, which means if I do go that route I will have some ground to make up. But c’est la vie.
Lastly, no ego boost. I know I have to work hard to achieve my goals and that is what I do. Thanks for the compliment though.
@Jeff,
“Supplements are inherently safe; prescription drugs are inherently unsafe.”
It would be more accurate to say that the average supplement is more likely to be safe than the average prescription drug. And that’s partly because drugs that have effects are more likely to have side effects.
Serious adverse event reporting is skewed. Huge numbers of people take prescription drugs and they are more alert to side effects and more likely to report them. When people assume supplements are safe, they are less likely to consider them as a possible cause of new symptoms.
A history of safe use doesn’t necessarily prove that a supplement is safe: problems may have occurred in a minority of patients and not have been recognized.
@nybgurs
“there is indeed a difference applying as an FMG from the Carribbean vs and FMG from Oxford”
Agree.
@SH
I’m a younger surgeon. Went through residency as the transition was made to the 80hr work week. Early on I went north or 100hr/week regularly, including one horrible stretch in the hospital from Friday at 5am to Monday at 8pm. By my cheif year my program was respecting it. All programs are now, because the ACGME (American College of Graduate Medical Education) has put some programs on probation for work hours violations. There are even more restrictions for interns now, and talk of a 60 hr work week (which is the standard in England, I think). The American College of Surgeons has seriously considered leaving the ACGME, and probably will if any additional restrictions are implemented. I guess that is a seperate discusion.
gears,
Yes, discussion tangent mostly over but I wanted to clarify my argument is not the naturalistic fallacy any more than your position is that we must stop consuming broccoli immediately and perform safety studies to establish no hidden dangers exist. I’m perfectly aware just because something is natural doesn’t mean it is safe by definition. The difference vs. novel compounds is that we already know this. We already know about nutmeg, we already know about strychnine, etc. We don’t necessarily know all about new drugs entering the market. For herbs, a more important issue is ensuring proper raw material testing and following GMP. These regulations are already in place for most countries though.
nybgrus’ comment that we don’t even know the ingredients in these herbs is also completely untrue. I’ve already referenced and addressed this in previous comments. Anyway, my point originally wasn’t even anything remotely like all herbs are all natural therefore all herbs are completely harmless. There are well-known potential dangers with certain herbs – herbs in pregnancy, herbs mixed with drugs, herbs with certain health conditions.
My point originally was that most of these things are already well known, that cases of lurking unknown dangers of use are extremely rare due to most things having made themselves apparent by now. How do I know this? I’ll quote nybgrus’ earlier “source” and say “the corpus of scientific investigation” around the world, including experts on the subject and government health authorities reviewing the evidence have come to this conclusion. This point was made purely as a contrast to some new compound just having come out of trials and entering the market. They are in completely different positions relative to human exposure over time.
Sorry Robb, but you don’t know. I gave the example of aristocholia as used for quite a long time and everyone thought it was safe until finally it was actually looked at and determined to be unsafe – very recently in fact. I will agree that for the most part, the majority of compounds in the majority of herbs and plants do nothing in the majority of people. But we don’t know which ones do and don’t and in whom. Recommending them therapeutically is thus not an ethically reasonable position, especially knowing that the vast majority of herbs and plant supplements have proven to have near zero if any effect whatsoever. With so many compounds from so many potential herbs and plants, giving it to myriad people is essentially guaranteed to produce negative outcomes overall (because positive outcomes are shown to be nil or small as I said, and there will be a subset of people who suffer negative outcomes). Don’t get me wrong – this is not a dichotamous argument. I am not saying that we should thus cram pharmaceuticals down people’s throats because they will inevitably be better. I am saying that we shouldn’t do anything unless we have a clear indication to intervene and an actual understanding of what the intervention will do, beyond some old wives tales of “traditional use.”
So your very premise that “most of these things are already well known, that cases of lurking unknown dangers of use are extremely rare due to most things having made themselves apparent by now” is simply false. The most obvious ones have become known. And even then some very obvious ones (aristocholia) still escaped scrutiny until just 7 years ago after thousands of years of use. You have no idea what less obvious dangers are still lurking, whom they may or may not affect, and every reason to believe that they are there.
It isn’t just me nybgrus, as I’ve pointed out. And your aristochlia example is an obscure counter example and an exception rather than the general rule. I’d never even heard of it before you brought it up – is it even available here? Kava would be a better example but most reviews I’ve read concluded that improper species selection, mould hepatotoxins, and health/lifestyle factors of the patients were the cause of complications rather than kava itself, which is why I brought up the GMP/QA testing point. I understand and appreciate your sense of caution. Let’s leave it at each case should be assessed independantly to get a better sense of what is known about it – whether herb or pharmaceutical.
It is not that obscure. It is common on TCM formularies and has had widespread use in China and yes, in the US as well. The “traditional use” stems from its resemblance to a uterus, so the TCM guys thought it was useful in childbirth to expel the placenta. That is “traditional use” and it was used since around the 16th century, with the most recent iteration being the 1999 Encyclopedia of Chinese Materia Medica which listed 23 species of Aristolochia… with no mention of toxicity. So once again, just because it has a “traditional use” and has been used widely for literally hundreds of years does not actually mean an herbal preparation is safe. But lets look at actual numbers. It was found to increase the risk of urothelial cancer by 50% (in addition to general nephrotoxicity). Wow! That’s a lot! How did nobody notice this? In 2008 there were 386,000 new cases of urothelial cancer worldwide. Out of a population of 6.7B that amounts to an incidence of around 0.006% (give or take a zero, doesn’t really matter). So if we increase this by 50% we get 0.009% (and that is assuming every single person on the planet consumed 200mg of Aristolochia daily). Do you see how small the signal is? And why it took so long to recognize it? A 50% increase in risk – which leads to such a small absolute risk increase – is still quite significant. That means that potentially an additional 193,000 people would get cancer and of those 75,000 would die.
Furthermore, it was noted that it was a cumulative effect of continued usage that really increased the risk, which makes a signal even harder to detect. Supplements are not under the same scrutiny as pharmaceuticals – as Dr. Hall pointed out. And even if they were, once again, we are talking about myriad compounds being ingested all with the potential to be deleterious and all with the potential to have cumulative (and synergistically negative!) effects. Aristolochia is just one example of how much “traditional use” means. Do you realize we used to give babies lead pacifiers for years until we realized how bad it was for them? How about smoking? That is an “all natural” herb with measurable physiological effects. How long did it take to realize how bad that was?
So yes, each formulation must be approached individually. The problem with a herb or plant is that you are taking a LOT of compounds at the same time. If there is a signal, you will have trouble pinning down the culprit. If it is a very small signal, it will take a large sample size to spot it. And if it is a very delayed signal, then it will be even harder.
Quite simply, the numbers are against there being an overall utility for herbal/whole plant extracts having a net beneficial outcome and for it having a net negative outcome. We all have to eat, so cutting out brocolli or steak is a stupid argument. But yes, there *are* toxins and carcinogens in your char-grilled steak as well and eating too much of it has deleterious effects as well. The best strategy – especially when discussing implementing something in a nation-wide health system – is caution. Because that tiny increase in cancer incidence will lead to thousands of deaths because you thought an herb was somehow intrinsically better than a pharmaceutical agent.
It amazes me that a person who presumes to be talking authoritatively about herbs, has never heard of aristolochia, to point even of misspelling it.
BillyJoe, I am glad to have amazed you. There is no edit function in comments so you’ll notice that sometimes people have spelling errors or grammar mistakes as in your own “to point even”. Do you honestly believe that people being knowledgeable about herbs = they must therefore have heard of ever herb in the universe? I’ll admit I do not know every herb in traditional Chinese use. Thank you for your fail troll contribution.
my other comment is awaiting moderation as it has three links. I do have to say though BJ that the spelling jab is a pretty weak one. I misspelled it as well, if you notice. It is an easy one to transpose the letters, even though I know what the latin roots mean.
However, it is a fair point that when making assertions about the safety of herbs and claiming that traditional use for a long time is sufficient to assert safety one should actually know about pertinent refutations to that argument before engaging in it. It is always much more impressive to say “Here is my argument, and here is where you might head me off, but this is why it is an exception.” But Robb merely asserts it is an exception in reaction to my evidence, without actually demonstrating why it is an exception or relating it to fundamental principles. The argument boils down to (at best) an absence of evidence of significant harms from herbals means that there is no harm from them, without actually discussing why there is an absence of evidence, what that could actually mean, nor the fundamental principles involved (law of large numbers being one, which is in my comment awaiting moderation). All the while he continually offers up exceptions to his own rule – “but most reviews I’ve read concluded that improper species selection, mould hepatotoxins, and health/lifestyle factors of the patients were the cause of complications rather than kava itself.” Exactly. If you made the basic assumption you are asking us to make, then no one would have reason to think twice about the species, handling, and health factors of patients taking kava in the first place. And as my soon-to-come comment demonstrates minute absolute risk increases from aristolochia means tens of thousands of additional deaths.
In law, one is innocent until proven guilty. In medicine one is dangerous and ineffective until proven otherwise for exactly that reason. I demonstrate that a potential 75,0000 additional deaths per year from cancer alone could be attributed to aristolochia… yet that signal is still so small it was very tough to detect unless one was specifically looking… and/or had a large enough sample size to pick up those deaths. Yet by the assumption that “traditional use” and “long term use” is a meaningful proxy for efficacy and safety we could be causing tens of thousands of additional deaths… with very little, if any, actual benefit.
I should add that Robb also self-contradicts within a single sentence:
“but most reviews I’ve read concluded that improper species selection, mould hepatotoxins, and health/lifestyle factors of the patients were the cause of complications rather than kava itself.”
Wait – the species is the kava. It demonstrates nicely my argument. In closely related species you can have some with deleterious effects… because you use the whole plant. Basing your assertion of therapeutic effect on traditional use means almost certainly a lack of highly specific species knowledge. So even then, you can’t claim “traditional use” gave you meaningful information and you can’t assert that “the kava itself” is not the problem when, in fact, the species of kava itself is the problem. Because that is what happens when you use the whole plant isnetad of determining which few – if any – compounds from it are actually the useful and non-toxic ones.
Oh f$&k, My posts are full of spelling errors. Let’s not start picking on those now, cause that’ll be the last straw for me.
@MTR,
There is no need for foul language in the discussion forums.
OK, so I’ll return to my broccoli example. Why then should we assume safety of anything? Efficacy is a different question. What is your gold standard of safety that trumps the “known scientific corpus of commonly used herbs” that I’ve been referring to: long term use in large populations, human clinical trials, animal studies, and known pharmacological actions of ingredients? Remember, I have never said long term use alone is what is being used to judge safety here – I said that long term use gives the herb a headstart compared to new compounds so they can’t be equated. So your Chinese herb that I don’t want to try and spell again is an exception because not enough was known about it – there was probably nothing but long term use to support it. Knowing the compounds and their effects, which we do for most commonly used herbs that I’m referring to, helps a great deal when it comes to potential toxicity, obviously.
Also, nybgrus, this doesn’t make sense: “In closely related species you can have some with deleterious effects… because you use the whole plant.”
It has nothing to do with use of the whole plant – it’s because you chose the wrong plant. The plant with different compounds/different effects.
I think we are talking past each other a bit Robb.
Lets limit your argument to your last most succinct and clear point:
I won’t belabor the point that we really don’t know the compounds, toxicities, and effects of most commonly used herbs. In part because “commonly” depends on context (what is common in China is not common here or in Africa).
But lets back it up to your assertion that “long term use in large populations, human clinical trials, animal studies, and known pharmacological actions of ingredients” is what you meant by “knowing” the compounds and their effects.
Superficially I certainly agree. But “long term use” is of such little use we can drop it from the list. The rest is purely pharmacognosy.
So then where are we? A plant with myriad compounds which we have now tested for safety and efficacy in animal studies, bench science, and clinical trials. Just like any other drug small (side) effect sizes need to be monitored in Phase IV. The problem we have is that instead of just 1 drug or 2, we have a whole slew of them. And as I have demonstrated serious but small effect sizes can be easily missed for quite some time. So in other words, we are doing the exact same thing as regular ol’ pharmaceutical testing, just making it more difficult since we are not controlling for single variables but for a slew of them (i.e. all the compounds in the plant). The assumption that if the initial effect is positive then that means there must be solely beneficial synergy from the rest of the plant compounds is simply false. There may be 10 compounds with beneficial synergy and 1 with a deleterious effect.
The next point is that the science of pharmacognosy has demonstrated that the effects we do see from beneficial plant extracts and compounds is usually not that great and the side effects are usually large. That is why we tweak the molecules to improve efficacy and decrease side effects. Taxol being a great example. Or vincristine. Or penicillin. Or any other such derived molecule.
Lastly, the notion that any novel pharmaceutical is completely new and therefore we can’t have any idea what it does is bollocks as well. The vast majority are derived from natural sources to begin with. And rational drug design is a very new and very difficuly process. But by definition and in practice the point of rational drug design is the target a specific molecule with extremely high specificity and thus is actually quite well known what it will do… at least to the same degree as a naturally derived molecule from a bench science perspective. Then going forward with clinical trials is the same no matter what the source of drug.
So no matter how you slice it, relying on something being a whole plant extract, or coming from traditional use, or long term use is of so little practical utility that it becomes rounding error. Truly, the only utility is that if people have been using something consistently there may actually be an effect, so it is not unreasonable to use that as a starting point since starting from a very low prior probability is better than starting from an extremely low prior probability (i.e. picking things at random). And of course, even that isn’t really true because of high throughput pharmacognosy screening which automatically searches for bioactive compounds in tens of thousands of sources constantly.
We simply have better ways of doing things than whole plant extracts, herbals, or supplements these days.
Nybgrus’ previous comment finally came out of moderation (I find this delay frustrating so I never put more than two links in any comment). He says, “Quite simply, the numbers are against there being an overall utility for herbal/whole plant extracts having a net beneficial outcome and for it having a net negative outcome.” A sweeping statement.
There are many examples of botanical extracts showing efficacy in clinical trials. In an earlier comment Nybgrus mentioned Saw Palmetto. Certainly the results for Saw Palmetto have been mixed. Two recent trials concluded SP extract relieved symptoms of BPH and improved sexual function:
1. http://www.ncbi.nlm.nih.gov/pubmed/22522969
2. http://www.ncbi.nlm.nih.gov/pubmed/21304222
Nybgrus also says, “The best strategy – especially when discussing implementing something in a nation-wide health system – is caution.” Fortunately in the U.S. we don’t have to wait for dietary supplements to be incorporated into a nation-wide health system. 1994′s DSHEA gave American consumers freedom of choice. They can do their own research and decide for themselves whether or not to try a safe, affordable product like Saw Palmetto extract.
Robb asked about aristolochia. Steven Novella blogged about it on April 11, 2012. You can find it by searching for this: ScienceBasedMedicine – Herbal Medicine and Aristolochic Acid Nephropathy.
Wow. An appeal to Saw Palmetto. Two much better studies were done in JAMA and the NEJM. Nicely summarized by Mark Crislip.
http://www.sciencebasedmedicine.org/index.php/the-prostrate-placebo/#more-16383
Link one is to an 82 patient, non-blinded, non-placebo controlled “pilot study”.
Link two is to a 120 patient, non-blinded, non-placebo controlled study.
Newer, crappier studies don’t trump older, more rigorous studies.
thanks for that jmb58 – I was just about to post the same thing.
How about a botanical that actually has genuine effects that are better than a pharmaceutical equivalent? Care to supply the research for that Jeff?
Boy. Really shot yourself in the foot with that one by demonstrating that you clearly don’t know how to actually research something for yourself, let alone the average consumer who has never even heard of “PubMed” or “Cochrane.”
Okay, I perhaps overdid it with the misspelling thing, but it was a secondary point in any case.
Here’s a recent meta-analysis concluding that Saw Palmetto is effective. The authors state their preference for SP extracts sold as drugs instead of supplements:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175703/?tool=pubmed
It seems to me a carefully prepared standardized extract sold as a supplement would be as effective:
http://www.jarrow.com/product/309/Saw_Palmetto_(Serenoa_repens)
As I said, the results are mixed for Saw Palmetto. It has an acceptable safety profile, with relatively mild potential side-effects, especially compared to available drugs. There’s enough positive data to make Saw Palmetto extract a viable option for someone with BPH.
Just a small side-issue, for interest, re this business of botanicals and species. It may have some relevance to arguing with those who believe a plant has been used for 100′s or 1000′s of years. See if it helps.
Identifying similar plant species (I do it daily) isn’t as easy as all that. Species can look remarkably like each other, even if they are unrelated.
It can be interesting too, to look at the old herbals, which recorded the popular uses of plants for medicinal purposes those 100′s of years ago. The illustrations are frequently crude to the point of being unidentifiable and the names are far from standardised, pre-Linnaeus. I wonder how anyone managed to use them, and how many herbalists just guessed and hoped for the best.
Those who are trying today to scan “traditional-use” plants for possible objective effects, are encouraged to deposit voucher specimens with a recognised herbarium, for this very reason. However, unfortunately, their supervisors and bosses seldom insist, and often neither do the journals they publish in. This may come back to bite them some day, if they do discover something useful but have no authoritative name for the plant, and no way of back-checking.
I maybe cited (just my pers. exp.!) this one before, but I had a couple of cancer researchers come by a little while ago, that wanted me to help find them some plants that were traditionally used. I couldn’t go with them every day that week, so sent them off alone, and some of the plants they brought back were so far off base it was hard to not laugh. But of course that wouldn’t have helped so I didn’t. I’d sent them off with photos and a description, but what came back in their bags wasn’t even in the same family, let alone the same species. Oh, and they’d never heard of keeping voucher specimens.
I’m a dyed-in-the-wool skeptic wrt medicinal plants, but I have to operate in a system that is not only replete with true-woo believers of the Californian variety, but 95% populated by indigenous-culture, our-ancestors-used-it-so-how-dare-you-disagree, folks. I’m trying me best to light a little candle, though how useful it will be I just don’t know. Thanks to you all for helping to light it up again when it gets blown out!
SkepticalHealth “There is no need for foul language in the discussion forums.”
SH – HH and DG gave YOU a warning and told you to tone it down. I’m assuming the rest of us can continue to behave as we have been.
Kathy – That’s interesting. It make sense to me considering the number of times I’ve purchase mislabeled plants at HomeDeport
Just out of curiosity… you post prompted me to check out “voucher specimens”. What are smart process, you’d think everyone would be onboard.
Michele,
I believe SH was being facetious.
Actuallly, no BillyJoe. I believe he was attempting to reframe his reprimand as a silly over-reaction to not-PC language.
But I don’t accept that reframing. I have never seen such a high level of venom against patients in any other commentor on this site. I think that is the problem. Not swearing.
Just IMO
@kathy:
Thank you very much for that insight! That is essentially exactly what I have been trying to say in my posts but much less eloquently since I am not as intimately aware of the issues as you are. I have taken (I think?) 3 botany classes in my life and the last one was 11 years ago.
But yes, that is exactly the point I was trying to make earlier that identifying the plants in question is not an easy task, if possible at all.
@mouse: passive agressive reactions are indeed very childish and best ignored.
ahem, one of the points I have been trying to say, amongst a number of them…. sorry. Just woke up and only halfway through my coffee.
@Jeff:
You don’t actually demonstrate your claim that “[people] can do their own research and decide for themselves whether or not to try a safe, affordable product like Saw Palmetto extract” when you continually demonstrate you haven’t even the foggiest of how to even begin reading a study.
It is not a meta analysis. It never claims to be. It is merely a literature review
And it does not conclude that SP is effective.
Analysis of the existing clinical database indicates that extracts of Serenoa repens may be considered a viable first-line therapy for treating LUTS…However, the existing herbal formulations are extremely heterogeneous and thus difficult to assess in meta-analysis. More randomized, placebo-controlled, long-term trials are needed in order to eliminate all scepticism related to the use of phytotherapeutic agents in BPH-related LUTS patients
As Dr. Crislip noted, GIGO – garbage in garbage out. Furthermore, this was published just prior to the JAMA article demonstrating no effect beyond placebo and thus wasn’t even considered. Furthermore you can see a clear bias of interest in the article – the authors start out by saying that the purpose of their work stems from “a revival of interest in phytotherapeutic agents.” They then proceed to blithely write off studies that demonstrated no effect of SP, including a a large systematic review in 2009, while touting other studies with poor methodologies such as a “trial [that] had no placebo arm” and one that “reported slight superiority of Serenoa repens” and another one that showed SP “improves urinary status by comparison with ‘watchful waiting.” Well, that last one sounds good at least, right? Well… except for the fact that they neglected to consider the study’s actual conclusion which was “All drug treatments showed some improvement over watchful-waiting for most patients over the study period: the alpha-blockers were found to be the most effective.” They also call these “studies with high scientific value” but neglect to mention that the last study, in which they cherry picked the wording, was not an intent-to treat analysis and merely a prospective survey study and just slipped in that it lumped together Serenoa repens and Pygeum africanum as the phytotherapy.
Also note that the study with the “slight superiorty” actually looked at multiple analysis with the two main end points showing p-values of 0.051 and 0.049… which does not really meet the criteria of significant, even from a purely frequentist standpoint. And the last study of “high scientific value” only looked at mild to moderate BPH and found statistically significant changes, but in many of them they would be clinically insignificant (a mean prostate size decrease from 39.8 to 36mL) and interestingly never once cite a single actual statistic in the entire body of the full paper.
Last point I will touch on:
No, no they don’t. They say:
Particular attention must be focused on differentiating between registered preparations, which are regulated as drugs, and those considered to be food supplements.
In other words, they note that there is extreme heterogeneity in what is actually available as SP (“the problem was recently raised in a meta-analysis, although the evaluation included studies of various durations as well as some on mixed herbal drugs consisting not only of Serenoa repens extract”) and that the registered varietes are more likely to actually be SP and have a little more evidence of efficacy.
The entire review is clearly biased in favor of phytotherapy and has nothing really interesting to add. They discuss the massive limitations in the studies, blithely lump in other herbals as if it meant nothing in the analysis, write of good negative studies in favor of bad positive ones, and obviously was published before the good negative study in JAMA.
In other words, nothing even close to demonstrating utility of SP.
And this took me roughly 22 minutes to write up in its entirety over my morning coffee. But that is because I have had a lot of practice doing this sort of thing. Perhaps you would like to demonstrate yet again your amazing ability to read and understand studies, when your opening sentence get the type of study wrong?
@Jeff,
You are severely out-classed.
@nybrgus – I believe that passive aggressive behavior is often best ignored, but I make exceptions for people who are either in a position of authority or posing as a person in such as position.
If I witnessed a teacher or a coach treating or talking about a child or teen-ager in a passive aggressive way I would deal with it.
A doctor is in a position of authority because they are a gatekeeper to a patient’s access to healthcare. If I see a doctor (or someone posing as a doctor) acting in a passive agreesive way to patients, particularily a patient population that has already experienced frustration with access to healthcare, I confront it.
Those are my ethics. I’m sorry if it ends up littering the board with off-topic comments, but so it goes.
Nybgrus, the study authors merely state a willingness to examine the data using plant extracts as an alternative to side-effects laden drugs. I wouldn’t call this a phytotherapy bias.
Their conclusion makes it clear they were analyzing studies as well as reviewing literature:
“Analysis of the existing clinical database indicates that extracts of Serenoa repens may be considered a viable first-line therapy for treating LUTS. They offer significant improvements of urinary status while having a favourable safety profile.”
“Nybgrus, the study authors merely state a willingness to examine the data using plant extracts as an alternative to side-effects laden drugs. I wouldn’t call this a phytotherapy bias.”
I would call it biased. Unless they also studied side-effect free drugs as an alternative to side-effects laden plant extracts.
@kathy,
Thin Layer Chromatography is what is used to verify a plant’s identity and its marker compounds. No manufacturer of herbal extracts is going to rely on visual identification alone. This is assuming they are relying on wildcrafted material or raw materials from another party rather than their own farms where identification would already be established.
Cigars and cigarettes are known to have physiologic effects on patients. They are not side-effect laden. Nicotene gum and lozenges, and varenicline, on the other hand, are side-effect laden. I think cigarettes should come with their package inserts. Then patients would find excuses not to smoke because of side effects. I’ll keep dreaming.
Jeff, the bias is the way they frame the studies they use as evidence for SP vs those that cite as evidence against SP. The ones for it have poor methodology (as I outlined above) and don’t differentiate between multiple herbal extracts yet still cite as evidence for SP. The actually good studies (which once again don’t include the slightly later JAMA study) are framed as simply being the signal in the noise, even though the methodology was superior.
Analyzing studies in the context of a literature review does not a meta analysis make. I should know – I recently co-authored a lit review on diastolic heart failure that is currently in peer review. A lit review doesn’t mean just listing a bunch of studies – any idiot can just type in key words and MeSH parameters into PubMed for that. It means putting into context and giving some analysis and discussion. This differs from a meta-analysis in that it doesn’t pool the studies together to give additional analytical power through complex statistical methodology. It even differs from a systematic review – that is when you create criteria and search for every single study in a specific time frame to analyze. It is more rigorous than a lit review but (much) less so than a meta-analysis.
So yet again my point stands Jeff – you are clearly not equipped and educated enough to review the literature and understand what it means to make an informed decision, let alone the majority of people who don’t post on medical forums and post up PubMed links. That is not an insult by the way – learning how to read and analyze these studies is actually rather difficult. I think I am pretty good at it, but boy do I have waaay more to learn! Many doctors don’t even know how to do it. It really does take significant time, effort, and education to even get a handle on it.
@Robb:
Mate, you are all over the place. What does TLC and having your own farm have to do with it? We may just have to start this over another time because you haven’t been able to put forth a unified, cogent, and coherent thesis as to what you are arguing. You keep wanting to hold on to this “whole plant extracts are better” thing, and yet keep having to concede various points without realize that they have thwarted your initial thesis.
I mean, you say:
Right… and….? How did they establish them? Why that particular plant? Where did they find out the information to decide to grow that plant and identify it in the first place before they started the farm?. Your rebuttal has no bearing on Kathy’s points.
In as distilled and concise a version as I can, here is where we stand:
1) Traditional use and long term use is not even remotely sufficient to establish efficacy and safety
2) Identification of which specific plant is the subject of traditional use is extremely difficult
3) Ergo, this means that not only is the farmed plant likely to not be the “traditional use” plant, but it is also likely that the “traditional use” plant is actually different depending on which geographic locale you ask, even in small areas
4) Once you have a plant that you wish to test, it still must be tested in the standard scientific manner
5) Testing multiple compounds at the same time makes scientific testing extremely difficult and rapidly unmanageable
6) Compounds in plants can have cumulative, late, or very small effects which have been demonstrated to lead to tens of thousands of unnecessary deaths and still go unnoticed
7) All things being equal, it is thus more desirable to have isolates of compounds and/or novel compounds being tested singly or in very small combinations in order to maximize understanding of effects and lend itself to monitoring for said cumulative, late, or very small deleterious effects
8) Therefore it is unreasonable to say that whole plant extracts are “better” than purified pharmaceutical compounds (no matter the origin) since “traditional” and “long term” use are essentially useless and all compounds must go through the same scientific testing.
Go back through our conversation and you will find that you have agreed with essentially every single bullet point I have listed above.
nybgrus,
1) I consider long term use one factor of many when it comes to safety. All else being equal amongst compounds, one that has already got a long history of use in large populations is meangingful in terms of safety compared to something brand new. I don’t think it is a factor for efficacy although you would hope people wouldn’t continue to use useless remedies generally.
2) and 3) I’m not sure how you came to this generalization. Yes, they didn’t have TLC in the past – just botany and Latin names to differentiate. Is it possible that the Matricaria recutita used today is not the same one described in traditional texts? It’s not impossible – but for most common herbs I think it’s highly unlikely.
4) Agreed
5) Difficult, yes. Unmanageable? I’d disagree and say you can’t generalize. Panax ginseng has many different ginsenosides all with different effects. They’ve been studied in isolation and in concert. It definitely makes the process of learning longer and more complex but there are herbs where the extra effort is deemed worth it (Rhodiola being another example).
6) Your Chinese herb theory that it led to thousands of unnecessary deaths? In cases where there is a long history of use of something of unknown pharmacological properties, then yes, possibly. As I’ve said, most commonly used herbs are not unknowns like this.
7) Ideally, I’d say standardized extracts with as many active constituents as it is feasible to use to get the best therapeutic effect. Stopping at one is not ideal in my opinion, based on known contributions of multiple constituents in herbs.
I don’t think whole plant extracts are always better than purified pharmaceutical compounds. I’ve said you can’t generalize. In some cases there might not be any advantage in isolating single compounds and in some cases there may be.
1) I’ve illustrated quite clearly how it is not even a reasonable factor. It only lets you know that something isn’t acutely toxic. You wish that people wouldn’t continue to use remedies when they do nothing, yet they do… constantly. Homeopathy, reiki, chiropractic, acupuncture, trepany (yes, drilling holes in your head is STILL practiced today), TCM, power balance bracelets, blood letting (not any more but for hundreds of years). The point is that it is vastly more difficult to detect and pinpoint deleterious effects than you think.
2/3)I suppose my confusion then is what do you mean by traditional use and how does it come into play? From the standard interpretation one would take it to mean that (for example) a village in China used [X] to treat fevers. It gets passed down for hundreds of years from village to village and everyone claims it works to great effect. They write a materia medica and include this herb in their TCM books and call it [X]. Researchers come and look in the book and try to find the plant… and there is where it all falls apart. Within a village it may be one species of [X], in another it is a different species. There is no differentiation. They take whatever it is that they have and study it. As we have seen, they typically demonstrate no effect or an effect different from what the traditional use claimed. And then we go down the rabbit hole.
4) Glad we agree.
5) Yes, it is vastly more difficult, as I illustrated above in how many studies you would actually need to do. Going to 5 or 6 compounds means thousands of trials to adequately quantify the synergistic properties. Is it possible? Yeah. Is it feasible? Not with our limited resources.
6)So I guess we are limiting your entire argument only to those yet-to-be-defined “common” herbs? How do you define common? Are you really asserting that every herb used in TCM (which would be extremely common based on the population using it in China) is extremely well characterized? Especially in light of my example of a commonly used Chinese herb? Your premise was that ALL herbs were better… now you are retreating to just the “common” ones that have their compositions fully elucidated (which I would still argue is a pipe dream)… but how did they get there in the first place? Certainly through no utility of the concept that traditional use and long term use mean anything more than “hey test this first”
7) And here is where it becomes unmanageable. How do you know how many is the ideal number to be synergistic and beneficial but not harmful? Seriously, I would love for you to focus only on this question and answer, in as much detail and using rigorous logic, how you will know how “many active constituents as it is feasible to use to get the best therapeutic effect.” Explain to me – in general – the experiments and trials that would be needed to come to this answer for a single herb, commonly used or otherwise.
Stopping at one, in and of itself, may not always be the best – I agree. Taking advantage of synergy is an extremely useful concept. I am trying to explain to you that a) there is absolutely no reason to thinks plants evolved synergy for us and b) determing synergy of compounds becomes exponentially more complex (well, even worse actually since the calculations for the amount of increased testing for synergy needs to be expressed as a factorial). So yeah, in the far future, we will be able to do that. Just not now.
And for many things a single compound actually IS best. As we become more sophisticated in our molecular targeting we really actually only want to activate (or inactivate) one specific receptor. When we target multiple targets there is a rational approach to it – we assume that these multiple targets will act in concert to further achieve the goal (antibiotics and chemotherapeutics come to mind). But even then we need to test it because the synergy can have wildly unpredictable effects even when we really, really know the effects of the single compounds.
You are vastly oversimplying the scientific process that you agree we need to undertake and overplay the likelihood that plant [X] evolved this beautiful molecular synergy so it can best help get rid of our cancer.
@Robb,
How many years was blood letting used as the standard of care before we learned that besides being completely useless, it is incredibly dangerous?
Getting one out of 20 right is not a great record to run on, just saying! And, having sanitary conditions probably has more to do with fewer diseases today than most anything. Do you all remember scurvy? yes..vitamin deficiency. Somehow, for some unknown reason to me, modern meds ended it there. Fact is, most (perhaps not all..but most) everything is a vitamin deficiency..that’s the reason for illness today…low immunity to them. Yes, that’s my hypothesis..and my experience, and it’s been proven to me time and again. Herbs contain vitamins/antioxidants and if used properly, are part of the solution. At the least, they contain more closely, what our living bodies need to fight off disease, what they are meant for. Not synthetic chemicals. …and, the “it’s the dose of the poison” doesn’t go over too well anymore, when over 100,000 people die each year from the “dose”..that wasn’t gotten right…imo nor the side effects and untold disease and damages caused by them, just to add more synthetic chemical concoctions to the mix. “First do No harm”..I believe doctors ..most mean well anyway..yea even you Skeptical : )..I only hope you all will come around to simply getting some other things right soon : ) Chris..perhaps look into pumpkin extract for Type I Diabetes, I think it’s something you might be interested in..http://www.healthcentral.com/diabetes/c/114/11209/blood-sugar?ic=1108
nybgrus,
2/3) No, your nice story is not what would be considered traditional use. It’s the equivalent of the game of broken telephone. If you want to read some definitions and criteria for traditional use that are being used, check here:
http://whqlibdoc.who.int/hq/2000/WHO_EDM_TRM_2000.1.pdf
http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/notice-avis-trad_claim-alle_sub-util-eng.php
7) This is really a question about what is most efficacious, right? So let’s say there is a traditional claim that
meets the criteria in the links above (the Canadian one is probably the best example because it is used to judge pre-market approval). To validate a traditional claim scientifically, it would make the most sense to start with the whole plant as it was traditionally used. So we are talking tea or alcoholic tincture. Do a study on whether the whole plant is effective for the claim. Now assuming the results aren’t a total failure, there is interest in what the individual compounds in the plant do. What are the main active ingredients? What do they do individually? How do they affect each other? What are the right proportions? Yes, I know the number of permutations increases exponentially the more active ingredients you look at. Yet it still is done. St. John’s wort is a good example where it was originally standardized for one active and then later more were standardized for as it was realized this would improve efficacy. Panax ginseng is also a good example where this has been done. It’s an incredibly complex herb with dozens of potentially important constituents yet that hasn’t deterred research.
http://www.nature.com/aps/journal/v29/n9/pdf/aps2008134a.pdf
http://www.nature.com/aps/journal/v29/n9/pdf/aps2008133a.pdf
My ideal example may take forever to find with that many constituents. More realistically, what happens is research into validating traditional claims, identification and pharmacology of major ingredients, and optimal levels of standardization of these active ingredients is found. The question is really one of how far you need to drill down to find something effective. St. John’s Wort has basically stopped at 2 standardized ingredients (hypericin and hyperforin) being enough to be effective while it is still acknowledged that other ingredients present but not standardized for (certain flavonoids) do affect bioavailability in a positive way. Maybe they will be standardized for next as well. It’s usually on ongoing process that continues even after some degree of effectiveness has been found.
I have no idea what you are talking about with your last comment though – I’ve said that plants possess some sort of intent or sentience in evolving their synergy for our benefit?? Don’t be silly. The happy coincidence of synergy between plant compounds that happens to benefit us is no more unlikely than plant compounds being able to interface with our chemical receptor sites in the first place. Stuff in nature just works out that way sometimes. Do you similarly question the mixture of gases that you breathe each day or marvel at the ridiculous number of fine tuned constants that astro-physicists tell us are required for the universe to exist at all? In context, I don’t find the fact that some plants happen to possess a synergy beneficial to us all that unlikely.
oh dear.
robb:
2/3) First off, it is a false dichotomy to discuss “alternative” or “traditional” medicine as opposed to actual medicine. The discussion, including in that PDF you linked, hinges on essentially saying that “traditional” medicine is just as valid as actual medicine. It isn’t. But that is a whole separate topic. But let me demonstrate how incredibly useless a construct it is that you are trying to go by (and the Canadian PDF as well).
From the PDF:
So, the long historical use has demonstrated the safety and efficacy, but somehow we need science to demonstrate more safety and efficacy? If something has documented scientific proof of safety and efficacy (S+E), then the conversation is over – we are done. And if A + B = B then A = 0, right? So if “traditional” S+E + “scientific” S+E = “scientific” S+E… what use is the “traditional” part again? In other words, it doesn’t matter if something is “traditionally” safe and effective, since the science trumps that no matter what. The way it is postulated here begs the question and says that “tradition” establishes S+E, but somehow it still doesn’t because we need scientific proof anyways.
From the defintion of “traditional medicine:”
Aristolochia was used by the ancient Greeks, Romans, and Egyptians. It is part of the Traditional Chinese Medicine materia medica which is the modern version of the Ben Cao Gang Mu, which was used for over 400 years and included the use of Aristolochia. It’s uses as a “birthwort” is documented in the 1st century CE. Illustrative of my point, the ancient Greeks and Romans used it as a “birthwort” for around 1,000 years and the Chinese used it for arthritis and edema for for around 500 years. This fits the definition of “traditional medicine” as your chosen document defines it.
So, which “sum total of the knowledge…” do we use to describe the “traditional” use of Aristolochia? Do the Romans win because they used it for 1,000 years? Is it safe because it has been used – documented and with great success – for 1,500 years? Well, science tested that one and found it to be lacking. It is neither efficacious (for ANY of the “traditional” uses) NOR safe. So once again, “traditional” S+E (says yes!) + “scientific” S+E (says no!) = no! not safe, not effective. Where does the “traditional” S+E matter at all?
7) Sure, I agree it makes sense to start with the whole plant… and then whittle it down to the best bits. You’ve described pharmacognosy and high throughput screening. But that has extraordinarily little to do with “traditional use” and “long history” does not actually establish safety. So how does this support your point that whole plants are better?
As for your studies linked note that they are both out of Southeast Asia, which has been identified in numerous studies as being completely unreliable with poor study methodology and rampant publication bias. If you look at ACTUAL studies and reviews on it you find that ginseng has no evidence of doing anything, as a whole or in parts.
So once again, not only is the research complicated, but these traditional use herbs have a long and predominant history of having no effect.
Even St. John’s wort has extremely mixed results, with pretty much all the positive studies coming from Germany and Cochrane forced to say that overall it looks like there is an effect “but it cannot be ruled out that some smaller studies from German-speaking countries were flawed and reported overoptimistic results.” And with extremely mixed results, especially in subjective outcomes assessments, that is equivalent (at least for practical purposes) as a negative. There are simply incredibly few herbs/plants that actually have useful effects without further refinement. And “affecting bioavailability in a positive way” has nothing whatsoever to do with safety and essentially nothing to do with efficacy. In doing pharmaceutical research the appropriate manner is to standardize bioavailability so it is not a confounding factor.
No you’ve completely missed the boat here. Going off on how the gasses and fine tuned astrophysics constants are not that crazy (the anthropic principle) has no bearing on plants evolving to cure our diseases. From an evolutionary standpoint it makes very little sense for a plant to evolve wanting to have its stems, leaves, and roots eaten. And in fact most plants evolved alkaloids exactly to prevent this. The opium poppy didn’t evolve to help our pain problems, it evolved to get animals high and fear eating the plant again. We harnessed it for a different reason. So yes, it is ridiculous and highly unlikely the a plant will have evolved a complex biochemistry suited to help a specific disease. That is why high throughput pharmacognosy has such an INCREDIBLY low yield.
How about you give me a list of your top 10 plant/herbs that have demonstrated actual efficacy and are superior in both side effects and efficacy than a standard pharmaceutical compound. If that is too hard, how about just top 10 with proven efficacy? Shouldn’t be too hard, should it? Considering how common that is and how much you know about this topic. I’m genuinely curious to see how many you will come up with.
Not sure if that “oh dear” was directed at me or not since it appeared before my moderated comment appeared. On the whole plant synergy vs. single isolated compound topic, this is another example of what I’m talking about:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059462/pdf/1475-2875-10-S1-S4.pdf
No, it wasn’t directed at you. I’ll read that when I have a chance. I’m actually out of town on a vacation weekend so it may be a bit before I can get to it. that should give you time to find those top 10 herbal compounds
@rustichealthy,
I truly appreciate your “theory” that all illness is a vitamin deficiency. Can you please define a mechanism by which hereditary spherocytosis is caused by a deficiency in vitamins?
RH:
Where have I commented on this thread? And how does that biased website substitute for the title, journal and date of the PubMed indexed paper. It is just a speculative editorial that has absolutely no references, and continues to prove you do not read the links.
@rustichealthy
As I surgeon, I take care of a lot of trauma patients. I was wondering, what herbs and vitamins should I be using to treat my patients? I have looked in the trauma liturature and there aren’t any studies I can find looking at trauma and herbal/vitamin treatment. Must be big pharma (or maybe big blood bank) suppressing these important studies.
Gun shot wounds to the chest continue to be particularly difficult. Do you think pumkin extract would help?
After all, scurvy (ie. vitamin C deficiency) was cured with vitamin C.
According to Trick of Treatment, the discovery that scurvy was cured with vitamin C is one of the earliest known uses of (very primitive) randomized trials. Ie, on the boats one group of sailors got the limes, another group got whatever, etc, and they saw which ones did not develop scurvy. It’s interesting that rustichealthy would pick that example, because the principles we learned there helped us learn what does — and more importantly does not — cause other diseases.
jmb. sorry, I didn’t take the time to specify things like that in my statement.
I actually meant internal illnesses..so prevalent today, like diabetes, hbp, cholesterol, candidas, skin conditions like acne & eczema, arthritis, osteoporosis..parkinsons, ms, alzheimers, cancers, heart disease, MMR, even pertussis….pretty much everything other than accidents, gunshot wounds, trauma… I do give great credit to modern med for. Of course surgery is needed..car accidents..broken legs, wars. etc..thank you
But, I should add..perhaps. nutrients can be given in most all those cases to help speed healing also : )
Chris..it doesn’t..I just thought you’d want to google it..perhaps ..to see if there’s something more to it. It’s what I would do anyway. Here’s a few other links that may be of interest..
http://diabetes.webmd.com/news/20070709/pumpkin-benefit-for-type-1-diabetes
7 — Asian pumpkin may help thwart type 1 diabetes, according to a preliminary new study from China.
The researchers studied rats. It’s too soon to know if the findings apply to people.
Normally, people control blood sugar naturally through a hormone called insulin, which is made by certain cells in the pancreas.
But in type 1 diabetes, the body’s immune system mistakenly attacks those pancreatic cells. That wrecks the insulin-making process, leaving blood sugar uncontrolled without insulin shots.
The Chinese study suggests that Asian pumpkin extract may help protect those pancreatic cells from the ravages of type 1 diabetes. The findings appear in July’s Journal of the Science of Food and Agriculture.
http://www.sciencedaily.com/releases/2007/07/070708193019.htm
Compounds found in pumpkin could potentially replace or at least drastically reduce the daily insulin injections that so many diabetics currently have to endure. Recent research reveals that pumpkin extract promotes regeneration of damaged pancreatic cells in diabetic rats, boosting levels of insulin-producing beta cells and insulin in the blood, reports Lisa Richards in Chemistry & Industry, the magazine of the SCI.
http://medicsindex.ning.com/profiles/blogs/pumpkin-could-replace-diabetes-injections
It would help in fostering good glycaemia and metabolic control
Prevents long term complications due to the antioxidant protection
It prevents the progressive destruction of pancreatic beta cells
Research done at East China Normal University highlights the fact that diabetic rats fed the extract had only 5 per cent less plasma insulin and 8 per cent fewer insulin (beta) cells as compared to normal healthy rats
The extract is good for pre – diabetic as well as those already suffering from it
Insulin injections still need to be taken, but the number of injections will reduce
Maybe you can ask your doctor.
Skeptical..I didn’t include ‘hereditary’ diseases..being more difficult of course..however, I did find this ..
http://www.freemd.com/hereditary-spherocytosis/treatment.htm
It looks like B vitamins and iron would help. But, I do believe, somewhere along the line, the cause was either a toxin or vitamin deficiency, thereby weakening the mother’s and baby’s health..and so things are ‘inherited’..but, in any case. I’m not educated in all the specifics of all diseases. Nevertheless, it would seem to be something as an exception to deal with. Wouldn’t you think it’s a good thing to actually eliminate, certainly minimize all of the illnesses I listed above? I’m sure your patients would appreciate it too. I did say “most all disease”…I didn’t mean every single one. It was a joke..1 out of 20..you’re not being obnoxious today..as yet Skeptical..I appreciate it
nybgrus,
You’re missing the point re: plant synergy and my other examples. You asked why should plant synergy exist. My answer was I don’t know but it’s not really that unusual compared to the many other fortuitous occurences that make up the natural environment. In my example of whole plant synergy in the treatment of malaria that I linked, obviously the plant did not evolve that combination for our benefit – it is luck. And there are many examples in nature of this “luck”. Some astro-physicists confronted with the mind boggling nature of the luck that allows the universe to exist at all start to get all theosophical about it – I’m not even going to go there as I’m agnostic and it’s irrelevant to our discussion. Point is, amongst the sheer number of plants humans have used, some do have these fortuitious combinations and while it may be a small percentage in terms of the whole plant kingdom, it’s not really that unusual in and of itself.
Bringing up “from an evolutionary standpoint, it makes no sense for plants to do this”, is also a misguided assumption. Are you really going to argue that evolution of a species is always in a vacuum? That there are no ocurrences of co-evolutionary traits in nature? It’s a whole different discussion though and one that is unlikely to have an answer – I don’t think we know why.
As far as your request for my top 10 most efficacious herbs – I’m not really taking homework assignments at the moment. I’ve mentioned a few already throughout the thread. For you, SJW has controversial efficacy, for others it doesn’t. Especially given that anti-depressant pharmaceuticals themselves have questionable efficacy to start with.
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050045
You’ll choose a study to make your point, I’ll choose mine:
http://www.ncbi.nlm.nih.gov/pubmed/22969004
Your bias will guide you as well – interesting that you chose the 2005 Cochrane review for SJW and not the 2008 one which came to different conclusions:
http://www.ncbi.nlm.nih.gov/pubmed/18843608
The author’s explain the difference saying:
“In previous versions of this Cochrane review (published in 1998 and 2005), included trials
were not restricted to patients with major depression, whereas the inclusion criteria of the
present study were restricted to patients with major depression. This is not to say that SJW is
ineffective in depressed patients who are not classified as having major depression. Rather,
this restriction helped to decrease variability in the analysis.”
We’ll argue about quality of studies, publication bias, inclusion criteria in meta-analyses, confounding factors, likelihood of endpoint “goal posts” being moved mid-study, whether you trust the country the study was done in or not, etc. etc. The real problem is that there are a lot of cases where the consensus is not “no benefit” but is rather “preliminary evidence exists, but more good quality studies are needed”. It’s definitely a work in progress. Just for fun though, for your own interest, I’ll leave you with these to dissect as well:
http://www.biomedcentral.com/1471-2318/10/14
http://www.ncbi.nlm.nih.gov/pubmed/18254076
http://www.ncbi.nlm.nih.gov/pubmed/21036578
Actually, on the topic of why synergy of secondary plant metabolites developed, while it may be “luck” for humans, it does make sense for the plant too. These metabolites play the role of attraction and inhibition of animals, insects, fungi, other plants, microbes, etc. and on the inhibition side it would explain why there is synergy amongst the ingredients in plant essential oils (antimicrobial effects) and on the attraction side for psychoactive effects. One paper looks into the latter while noting the similarity in roles of neurochemicals between humans and insects.
http://advances.nutrition.org/content/2/1/32.full.pdf+html
http://www.mdpi.com/1420-3049/17/4/3989/pdf
@rustic
On another thread you say that you rely on us ignorant MDs for the diagnosis. Then you use nutrition and vitamens to unlock the body as a healing machine.
So we are fine for diagnosis, but not treatment. Except for injuries, then we are okay for treatment. But only injuries on the outside? You’ve got the “internal illness” covered.
What about internal injuries? Who should treat those?
Why the distinction with injuries? Injuries are just a type of pathology. Why is this the only type we can treat and you can’t? So if a knife injures the colon I can fix it. But if it is cancer in the colon, a big chunk of colon cancer I can see clear as day on the monitor (during colonoscopy), then I’m lost but you are all over that. I believe you stated it’s easy. What if the immune system has attacked the colon and eroded a hole in the colon wall, internally. More pumkin extract?
You mentioned you treat internal illness, like cancer. How about skin cancer? Not really internal. What do you do with a growing cancerous lesion on your arm? Have an MD diagnose it then take a vitamen? What if it’s a basal cell carcinoma that is almost completly cured with excision? Cut it off or more pumkin extract?
“nutrients can be given in most all those cases to help speed healing also”
Nutrition would be a better word. I spend a lot of time following the scientific studies related to nutrition in the injured patient. If there is evidence for improved outcomes, I implement the therapy.
Two examples of synergy among plant constituents:
1. Scientific evidence for synergy in a botanical product:
http://www.sciencebasedmedicine.org/index.php/scientific-evidence-for-synergy-in-a-botanical-product/
2. catechin-polyphenols and caffeine in green tea stimulate thermogenesis in rats:
http://www.nature.com/ijo/journal/v24/n2/full/0801101a.html
I love that rustic just blamed a vitamin deficiency for a hereditary disorder. Why are any of us entertaining this person?
@SkepticalHealth,
“I love that rustic just blamed a vitamin deficiency for a hereditary disorder. Why are any of us entertaining this person?”
Good point! He actually said “I do believe, somewhere along the line, the cause was either a toxin or vitamin deficiency, thereby weakening the mother’s and baby’s health..and so things are ‘inherited”
Does he think vitamin deficiency somehow causes mutations? Or is this some distorted interpretation of what epigenetics means? And why does he put “inherited” in quotes? Oy vey!
jmb..it’s certainly up to you and the patient how you wish to treat something. cut it out, if that’s the best you and your patient decide. I’m not determining that for you. As far as skin cancer is…I’d look up first, for myself that is, what if any natural treatment there might be. I’ve tried various things on different rashes..coconut oil works great, so does applecider vinegar, and baking soda! none of those I am kidding about! someone used ACV for her hemorrhoid…. I was mentioning it to take acv, but she actually applied it…and it worked! Of course skin cancer is another issue..I might even look up baking soda for it..and I’m not kidding about that either. You all need to open your minds to different ways of curing things..just because it was not taught in medical school..doesn’t mean it can’t be so!. Someone wrote not too long ago in CL how her eczema, that she had for a lifetime, was helped finally, with applecider vinegar and water..waiting 15 minutes then showering it off. I just typed in vitamins for skin cancer, and A, C and D all look very helpful..which would tell me now..it’s a deficiency of A, C and D..people are not getting enough of those vitamins. I would then go at it both ways..take the vitamins, administer whatever natural remedy..(baking soda I would try first personally)…it’s like going to war..if you mean business..you send in all you have. That’s how I would deal with something. Internally, find out vitamins lacking..externally, natural wholesome remedies..that have worked for others, and see if they’ll work for me. Basically, that’s my way of doing things. My son had bad allergies for years..over 10 I would say. ..sneezed and congested constantly…then he started organic diet, organic bee pollen, and basic vitamins C, D, omegas..and within perhaps 2 months gradually, he stopped all sneezing/congestion.
As far as accidents, injuries..etc..I think you know, I would depend on surgeons to fix it…but then I’d take vitamins to help with the healing also. I know you’re being facetious..I do understand the difference of what I can and can’t ‘fix’. like a broken leg..just how to help it along also.
Dr. Harriet..my premise of lack of nutrients..or..too many toxins..is to me plausible, since our bodies cells change because of illness, and so, quite possibly, if the mother is ill, is weakened in some area, and so the baby born will be weakened because of it in the same, if not then another area. I thought that’s how it would go..because of the close physical contact…growing, within the mother, why the baby is effected if the mother drinks/smokes..etc.. and….I’m a she
Harriet Hall – NTD and folic acid
http://www.chg.duke.edu/diseases/ntd.html#anchor2
also CLCP and folic acid
both seem to have a heriditary component.
@mouse,
He linked to an article on the treatment of hereditary spherocytosis and his comment clearly indicated he believed that that particular condition was caused by a vitamin deficiency. It isn’t: it is caused by an abnormal gene inherited in an autosomal dominant pattern.
Folic acid supplementation can reduce (but not eliminate) the risk of several congenital defects, but the mechanism is not genetic: defects result from interference with embryologic development. Folic acid deficiency does not cause mutations or inheritable diseases.
HH – agreed RH is confused. But it’s good for any readers to be clear that a nutritional intervention (folic acid) does lower the incidents of NTD significately and probably CL/CLCP moderately (but not cleft palate in isolation), both of which have a hereditary component.
I’ve seen a few comments in the past (rarely) saying something to the effect of “I’ve always been skeptical of those prenatal supplements”
Maybe I’m being over cautious, but I didn’t want an important health message to be accidentally muddied in the wrangling with RH.
@MTR,
When we refer to a disease as being hereditary, we almost always mean that it is acquired through a defective gene, and we usually know which gene is responsible for the disease, and the patttern of inheritence. Hereditary spherocytosis, cystic fibrosis, Marfan’s syndrome, and sickle cell are all examples of these diseases.
Other diseases, like NTDs and CL, along with diabetes, hypertension, heart disease, psychiatric conditions, many types of cancer (and there are heridtary forms of cancer, too!), etc, may have a heridtary component – that is, if someone in your family had it, you have an increased risk of having it too, but there is no definable pattern of inheritence where we can predict with reasonable accuracy, or do a genetic test, to determine if the patient will have the disease or not.
@HH,
I was curious if rustichealthy was going to try to say something like “if they had better vitamins, the DNA would have copied itself better and not had mutations!!”
@rustic
“it’s like going to war..if you mean business..you send in all you have.”
If you mean business you don’t waste time and resources on stuff that doesn’t work and/or makes no sense. I don’t see the Air Force adding natural, organic jet fuel supplements to their F-22s, or the Army incorperating ancient Chinese military technology.
“..I do understand the difference of what I can and can’t ‘fix’.”
No. You really don’t.
Baking powder is very cheap jmb..so are vitamins comparatively.. and they have worked for me and some I know..I’m not here simply spouting out things I haven’t tried! actually, they’ve proven very effective! I just wonder how you all Know they don’t work? without even trying it for yourself? That kind of puzzles me. I mean..’scientifically speaking’..shouldn’t you want to find out something for yourself? I didn’t know until I tried. I do know I can get myself off of 4 asthma meds including steroids…and arthritis without without any pain meds. Those are small things I know..imo too..but, that’s why I’m amazed at how still prevalent they are today..with no end in sight, in conventional medicine.
RusticHealthy, is it baking soda or baking powder that does wonders? They are two completely separate chemicals.
So what does baking soda work for? What is that evidence?
And what does baking powder work for? What is that evidence.
Why should we try “something for ourselves” when you cannot even keep your stories straight? Are you the person on this planet with the specific genome that defines the reaction to every protein or chemical on this planet? Do tell us. What makes you so unique that we must all react to the world like you?
I have a severe allergy to nickel. If I touch a hand sewing needle coated with nickel I get a rash on my hands and my feet. Does that happen to you? My sensitivity to nickel is so bad that I cannot touch cheap gold, which is hardened with nickel (even the stuff from Tiffany, and I have asked). I also react to chrome. My feet get a rash from how much I touched the chrome trim of a boat we rented at a lake. So unless you have a severe allergy to nickel and get sick to your stomach from all narcotics, your personal experience means nothing to me. Plus I have been vaccinated for yellow fever, typhus, typhus and smallpox, and survived dengue fever. Has that happened to you?
At least I know that the real doctors I talk to acknowledge my sensitivities. My family doctor also has issues with nickel allergy, and the clinic who did my colonoscopy was willing to deal with my narcotic sensitivity issues. At least there are some who understand why I am confused at those who would rob a pharmacy to get Percodan (why would anyone rob a store to get something that makes you vomit?), and they are often MDs.
RusticHealthy, you are unique. Your experience only speaks for you. Plus you need to open your mind in order to relate to others around you. That requires that you open your mind and learn about the world. Go find your local community college and learn the basics in science, math history and literature. Because you seem to not know anything beyond yourself. And that is a very lonely place.
Aagh.. ” yellow fever, typhus, typhus” should be ” yellow fever, typhus, typhoid” All diseases that RusticHealthy never had to worry about since she has probably never left the USA.
On the other hand, I get to now fear going to the Florida Keys because dengue has occurred there. The “fun” thing about actually surviving one of the four known versions of dengue fever is that if I get another of them my chances of getting a deadly hemorrhagic version of dengue fever has increased. Woo hoo. I am sure RusticHealthy will now come up with a vitamin I need to take to prevent bleeding to death from a mosquito bite.
@Chris: Thanks for including literature, but I feel RH would end up accusing contemporary American poets of not being close enough to nature (even Gary Snyder), boring his classmates by proselytizing Traditional Chinese Poetry, which will have nothing to do with Li Po (and everything to do with Jane Hirschfield), while completely ignoring (or essentializing) contemporary Chinese poets like Bei Dao or Wang Ping.
Chris : ) sorry…baking Soda..my son rubbed it in his bad case of poison ivy one time, and it went away .
I did see something about apple cider vinegar also for one’s nickel allergy..
http://www.skincell.org/community/index.php?topic=9511.0
This is on baking soda…
http://www.care2.com/greenliving/baking-soda-is-good-medicine.html
Chris..I know I’m unique..everyone is..something may work for some, not for others.
also, I’d mention vitamin deficiency..but I know you’re not open to it..I’m open minded…but, I like natural whole remedies as much as possible anyway..thank you : )
well..I will mention..Vit. D3 ..for dengue ..just fyi..
http://www.sciencedirect.com/science/article/pii/S0166354212000393
Chris..I have an aloe plant I bought a few weeks ago, and it turned brown ..really bad..I looked it up..and it said it was a ‘fungus’..I read somewhere baking soda is an anti-fungal..so I sprayed it with baking soda and water. Wiped it off..one time..and it’s totally green now! just wanted to let you know..since you’re growing organic.
and, I didn’t mean to say Every disease, I think I said most..but, looks like B vitamins for Typhoid/typhus, and honey, cloves and salt would be good to have around
http://www.online-vitamins-guide.com/dietary-cure/typhoid.htm
and, much more on Baking Soda..
http://wakeup-world.com/2012/05/07/51-amazing-uses-for-baking-soda/
is it against the conventional medical law to try some safer natural remedies? that’s the impression I get
@robb:
I am back from my mini-vacation and would have left the conversation if it hadn’t been for 2 things: that I am working odd hours in the ER this week and thus find myself with time on my hands and the genuinely poor attempt at chucking up studies by Robb.
From the beginning:
No I didn’t. I asked why would plants preferentially evolve synergy that is specifically useful for us?
You answer the question correctly though:
Yes, it is. But you also make the fundamental error at the heart of our discussion:
It is that unusual. Which is why there are orders of magnitude more failed attempts at drug synthesis and isolation and so few herbs with any actual efficacy… relative to the number that exist and that have been tested. It is a very low yield field. As for comparing it to “many other fortuitous occurences that make up the natural environment” this is a non-starter and an evidence free statement. What “other fortuitous occurrences?” The fact that physical constants are so “precise” down to the 19th decimal point? We have no frame of reference for the denominator on that and therefore any assumption as to its likelihood is pure and unadulterated guesswork. Additionally it is a pointless statement. Saying something is “common” relative to incredibly “uncommon” things proves nothing. I agree that finding herbs with curative compounds and synergy is more “common” than fatal famililial insomnia and vastly more “common” than a marble statue moving due to chance alignment of quantum states. So?
And to top it off you can’t even hold a coherent argument in your own single paragraph as you close with:
So which is it? Is it “common” or is it actually a “small percentage?” Because by any standard working definition things that are “common” have a “high” percentage chance of occurance. Things that are uncommon are the ones that have a small percentage chance of occurance. Since your entire argument up to this point has been about how useful and common whole-plant synergy is, I think we can reasonably end the conversation here on your own admission.
That’s funny. It is so common, and there are so many examples of this “luck” yet the “homework assignment” is too arduous a task? If you asked me for 10 things to support something I am asserting – especially something as straighforward as simple examples such as these – it would be trivially easy for me to reference them. I had assumed that since you seem to assert with confidence that whole plant synergy and the efficacy of herbs is a simple statement of fact, a common phenomenon, and easily demonstrable that you were actually familiar with the relevant literature on the topic and that just a few clear cut and unambiguous examples would be easy to throw in my face. Seems not….
If studies are mixed and equivocal, with some showing efficacy by the majority of them showing little, if anything, that is by definition controversial. You don’t just get to focus on the minority that demonstrate efficacy and claim that means there is a consensus on efficacy.
First off, complete non-sequiter. Whether pharmaceutical anti-depressants work or not is completely irrelevant to whether SJW works or not. Furthermore the study you linked is limited to only 4 of the newest generation of drugs. And as Jerry Coyne points out there is evidence that on the whole anti-depressants are indeed better than placebo and that studies in that field are either lacking or of very poor quality. Both references point out that depression is highly responsive to placebo, which makes sense, and further makes those few positive studies of SJW more likely to be an abberation of placebo effect in poorly controlled studies than a real effect.
But fine, I’ll give you a freebie – SJW works. How about 9 more, since it is “so common?”
A study on Panax ginseng which I can only assume you tossed up to try and refute my other studies which demonstrated no effect from ginseng. Funny that the second line of the abstract is:
“However, there is no conclusive evidence supporting its use in the treatment of any particular disease.
I ask for evidence of efficacy of herbs and plants and that is the best you can toss up? They found 475 potential articles on the topic and only 65 were good enough to include and of these there were 12 different systems studied as PG having a possible effect. And too boot the abstract goes further to say “The risk of bias was unclear in most studies” And out of all of that they pull out that there might be benefit of PG in glucose metabolism and immune modulation – of which there are 6 and 4 studies respectively. So 475 articles, of which 65 aren’t crap, of which 10 show the possibility of having an effect on two completely different systems by one herbal supplement, all the while with caveats that there is no conclusive evidence supporting its use and that the risk of bias was unclear in the studies used.
That’s some powerful science you are throwing at me Robb.
Not bias – just didn’t come up in my search. Mea culpa. That said, your link actually doesn’t say anything fundamentally different but does has a slightly better spin to it:
Here is the summary of the same Cochrane review you linked by the same authors that say the same thing… again… as my previous comment:
“However, findings were more favourable to St. John’s wort extracts in studies form German-speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries St. John’s wort extracts seemed less effective. This differences could be due to the inclusion of patients with slightly different types of depression, but it cannot be ruled out that some smaller studies from German-speaking countries were flawed and reported overoptimistic results.”
From the original Cochrane review you posted we can note a few interesting points.
1) “Results of placebo-controlled trials showed marked heterogeneity”
2) Larger trials showed a smaller effect size than smaller trials (1.28 vs 1.87)
3) “Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum.”
So we see a decrease in effect as trials get bigger and better, the trials actually testing the efficacy of SJW are “markedly heterogeneous,” and we still see the effect I pointed out previously that German speaking countries seemed to have a bias shifting the effect size up.
Once again, hardly a slam dunk for SJW here….
Preliminary evidence always “exists.” That is why it is preliminary. Because it is early, typically much more sloppily done, and usually does not pan out in bigger more robust studies. Besides, you have been arguing that the synergy and efficacy of herbals and plants exists not that there is some preliminary data to support thinking that they might exist. There is a big difference. And if you go through and read this blog and other science blogs you will find a common theme – that the phrase “more good quality studies are needed” is a catch all reflection of the shortcoming of EBM, whic is why SBM became the coined phrase around here. In fact, Cochrane has even taken notice of SBM’s critiques and taken notice. “More studies needed” =/= evidence of efficacy.
As for fun dissect:
Effects of Ginkgo biloba in dementia: systematic review and meta-analysis:
In the meta-analysis, the SMDs in change scores for cognition were in favor of ginkgo compared to placebo (-0.58, 95% confidence interval [CI] -1.14; -0.01, p = 0.04). If the CI contains zero (or 1, depending on the scale used) then we can consider the results to be more or less null. Granted, in a pedantic sense 0.01 does not technically cross that threshold, but it is close enough especially when dealing with something as subjective and difficult to assess as dementia. Additionally, as PZ Myers pointed out, that the significance threshold of 0.05 is arbitrary and data demonstrates that, particularly in psychology journals, there appears to be a clear bias to push the p-value just over that line with a massive spike in papers with a p-value just under 0.05. So especially in this context I find a p-value of 0.04 to be unexciting. But I am not just being a nitpicky a-hole here. The study goes on to say ” but did not show a statistically significant difference from placebo for activities in daily livin” and once again “Heterogeneity among studies was high” and of course the crux hinges on “For the Alzheimer subgroup, the SMDs for ADLs and cognition outcomes were larger than for the whole group of dementias.” Subgroup analysis to find significance when the whole group shows none or a very small effect size is the easiest way to make effects appear like magic. Even the conclusion is underwhelming:
Ginkgo biloba appears more effective than placebo. Effect sizes were moderate, while clinical relevance is, similar to other dementia drugs, difficult to determine.
Next up we have Hawthorn extract for treating chronic heart failure.
I’ll agree that this demonstrates hawthorn has some effect on blood pressure and cardiac load. So does foxglove. However, the review does not compare hawthorn to actual heart meds, only 7 of the 14 included studies actually say whether patients were using standard heart meds at the same time, and the conclusion is that it could be a useful adjunct to existing therapy by lowering the necessary dosage of heart meds. It also notes that there is no demonstrable effect on mortality or morbidity at all. And a newer study “…does indeed demonstrate that [hawthorn] is not a harmful therapy, but it’s one that is not particularly helpful nor that would be recommended,” Fonarow said. “It’s naturally attractive to think there is something over the counter or naturally occurring that may help improve outcome. Unfortunately, we’ve not been able to identify that so far.”
So we have one example of efficacy of an herb. With the gimmie from before that makes 2. But this one seems to also demonstrate that actual pharmaceuticals are a better option than some leaf tea, especially considering how many comorbid conditions CHF patients have and how much interaction is possible with a whole plant extract of hawthorn. Still waiting for 8 more… and then still some evidence that they are better than the equivalent pharmaceutical.
And the last one, The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomized clinical trials. which is a convenient one since my post-grad, pre-med research was on…. Rhodiola.
In other words lets get a whole bunch of stuff and dredge the data to see if we can come up with any correlations.
And out of all of that they come up with:
“R. rosea may have beneficial effects on physical performance, mental performance, and certain mental health conditions. There is, however, a lack of independent replications of the single different studies.”
You keep swinging for the fences with these studies offering resounding support of your thesis that efficacy of whole herbs/plants and synergy are “common” and “well established” and that “traditional” and “long term” use are useful indicators of this.
That said, I did actually do research on R. rosea. And in my fly models it did have a genuinely robust effect in increasing their life span and it did so independent of an anti-oxidative pathway (which makes sense, since anti-oxidation as an anti-aging strategy is simply not panning out in the literature, but back when I designed and did my assays it was a legitimate question). That is called preliminary data and my PI was bombarded with journalists and TV people asking her to talk about this amazing new drug that would extend life. She was very, very clear to point out that this was preliminary and in flies. And so the research continues to isolate the compounds (yes, plural because it was in her classes and her labs that I learned the most about synergy which you claim is a concept denied to exist for some reason) that are active and responsible for this effect. And then see how it might be applied to humans. It really is exciting research and deserves more study.
But none of this supports your central thesis that these effects are common, are better than purified and modified pharmaceuticals, or that more than a handful of herbs have an actually demonstrated efficacy.
BTW – you could have said Papaver somniferum or Erythroxylaceae erythroxylum as plants with proven medicinal efficacy. But, as was pointed out before, there is a very good reason why opium poppy and coca leaf is not available OTC at your local herbalist and why even in medicne we use derivates of the active compounds instead of just growing a garden of poppies on the roofs of hospitals to administer to patients.
nybgrus,
You are once again misquoting/misunderstanding my points – maybe my wording was poor or maybe the convolutions of the comments generally interfered. I wouldn’t say that I have a “thesis” for starters, but with regards to synergy, I don’t recall or see in recent posts me calling it “common”. I said it was probably a small percentage of available plants that displayed any kind of synergy beneficial to humans but that, plant synergy, as a concept or strategy, is not that unusual. I didn’t mean known cases of it being beneficial for humans was common statistically speaking, which I thought should be obvious from the first part of the statement. It is “lucky” when it occurs in beneficial ways to humans but as my follow up post brought up, it likely evolved as a response to insects, with cross over relationally to humans. As I’m sure you know it is also infinitely harder to prove or research and it’s impressive that there is more and more evidence coming out in favour of it.
The discussion on synergy was different to efficacious herbs as a whole though – although it is one argument for why you would select multiple compounds at least vs. single ones. You somehow leapt from misunderstanding “not unusual” to common to me somehow saying clinically proven efficacious herbs were common? I said no such thing. I’m well aware conclusive studies are lacking and that “preliminary evidence” is the norm outside of a few examples that came up.
I completely agree that ““More studies needed” =/= evidence of efficacy” and by the same token, lack of evidence =/= lack of efficacy. I’ve also repeated multiple times that generalizations aren’t helpful here. Your coca leaf example is a good case where the isolated cocaine alkaloid is more dangerous and acts quite differently compared to the whole leaf.
9/26/12 17:47:
Otherwise it seems we more or less agree. And I think you may be correct that you did not actually assert that clinically proven efficacious herbs were common. My apologies for putting words in your mouth.
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