Efficacy ratings thus tend to be conservative, as almost no trials of botanicals can afford to include several hundreds or thousands of patients. Cranberry for UTI prevention and hawthorn for CHF, both of which just got favorable Cochrane reviews, and ginkgo for dementia and memory impairment are rated as “possibly effective.” “Possibly effective” therefore really means that there is some pretty decent evidence. (Notably, they rate glucosamine “likely effective” for knee osteoarthritis.) If there have not been human RCTs (as will be the case for most plants not popular in Europe, where most good research has been done), a product will fall into the “insufficient information” category. Your count has 60% in that category; of the remaining 40% that have enjoyed human studies, apparently 37% had positive study results, and only 3% were found to be possibly ineffective or ineffective, meaning that of products studied in RCTs, *90%* had positive results for at least one use. Presumably, the “best” products – those with the most animal and in vitro studies and human experience data or popularity – are more likely to receive the very limited research dollars, so the remaining 60% might have lower efficacy rates. Still, this indicates that people are buying the “best” products for the very rational reason that the products are helping them.

Then there is the safety question. Their “likely safe” and “possibly safe” ratings largely parallel the effectiveness ratings. To be just “possibly safe,” “reputable references” must agree on the fact, and there must be “sufficiently rigorous human studies reporting no serious adverse effects.” (Again, human experience doesn’t count.) “Possibly unsafe” means “There is some evidence [what kind??] suggesting that use of the product might be unsafe,” and “likely unsafe” means “Reputable references or reliable literature report that the product can be harmful, based on human studies or reliable case reports of significant adverse effects.” This is a conservative standard both for “safe” ratings, which require expensive research to have been done, and for “unsafe” ratings,” which may be based on human experience, anecdotes, or speculation. Where some “unsafe” ratings are concerned, an even more conservative standard may have been followed, as I note below. The highest rating given to honey is “Possibly safe…when used topically”; no rating for food use is given, except “Possibly unsafe” for children due to infant botulism. Pumpkin seed, another FOOD, is rated “possibly safe.” Your numbers for safety total 102%; taking your numbers that 81% were rated, and 63% were found to be likely or possibly safe versus 18% at least possibly unsafe, this indicates that we can feel good about the safety of at least 78% of studied products. The potentially unsafe remainder include things like hydrazine and Lorenzo’s oil which are not typically sitting on the shelf at your local Whole Foods. Since FDA has the power to ban products that can be proven to be dangerous in ordinary use, and since regulation or fear of litigation has largely removed the botanicals with narrow safe dose ranges from the market, the products remaining tend to be pretty safe.

(A huge number of botanicals, including GRAS food plants, are listed as “likely unsafe” in pregnancy – and lactation! – based on three books that list them as possibly inducing or affecting menstruation, with no citation whatsoever of any anecdote of harm in humans. Food plants in this category include peppermint, flaxseed oil, and thyme. The books cited did not get these concerns from scientific evidence, which largely does not exist, but from compiling those “age-old beliefs” that the NMCD team elsewhere sneers at. Garlic is said to be “possibly unsafe” in pregnancy even though there are no published anecdotes of adverse effects, and a human study in pregnant women showing no adverse effects. Thus, the authors really did not live up to their own guidelines, making their protestations of a total lack of bias seem doubtful.)

“The Fever Trail, In Search Of The Cure For Malaria” by Mark Honigsbaum, Farrar, Straus & Giroux, 2001 illustrates the very real difficulties encountered when trying to introduce a botanical that is an effective drug into the practice of medicine.

Likely safe 38%
Possibly safe 25%
Possibly unsafe 6%
Likely unsafe 8%
Unsafe 4%
Insufficient information 21%

Effective 5%
Lilkely effective 6%
Possibly effective 26%
Possibly ineffective 2%
Ineffective <1%
Insufficient information 60%

That sounds better than it really is. Almost all the natural medicines rated effective and safe are vitamins, minerals, and products also available as prescription or over-the-counter meds approved by the FDA.

When you consider that only a small percentage of promising new drugs make it through the testing process and are marketed, what are the odds that a natural medicine picked at random from this database will turn out to be safe and effective when adequately tested? Then, what are the odds that a purified active ingredient might be safer and more effective than the original product (as with aspirin and digitalis)?

Add that to the many reports of contaminated products and content not corresponding to labeling, and it seems to me that taking one of these inadequately tested products is risky. Some of us are more willing to take risks, but don’t you think at least consumers should at least have access to the best available information?

Let me try again. The discussion was about dietary supplements, and by legal definition silver supplements are classified as “dietary supplements” in the US, a term also used for them in other English speaking countries. People who call themselves “alt. med. practitioners” sell silver supplements all over the world and claim that silver is an “alt. remedy”. Silver is also sold as a dietary supplement in health food stores right along with the botanicals.

The supplement industry has tried hard to make sure that silver supplements can continue to be legally sold in the US as “dietary supplements” in spite of the fact that the industry knows they are useless and dangerous while at the same time that very same industry claims that the public must have free access to whatever anyone wants to make in his garage, call a dietary supplement and sell to the public because they insist that supplements offer great health benefits. Because of this, I have a very low opinion of the supplement industry.

Now if you jump to the conclusion that I want silver supplements banned, you will be incorrect. What I want is truth in advertising. I want silver supplements to be required to carry warnings about argyria and statements to the effect that scientists who have studied them conclude that they are useless. I want similar factual disclosures on all supplements. But I assure you that that is not what the dietary supplement industry wants which is another reason why I have a very low opinion of the industry.

I want people who commit fraud in advertising prosecuted and given penalties that will serve as deterents and I’m tired of hearing you say that the FTC has the authority to prosecute and that you wish it would while you continue to ignore the fact that it lacks the resources to do so especially under DSHEA which of course is exactly how the supplement industry wants it and another reason for my low opinion of that industry.

You said, “I hope your suffering will not lead you to believe that anyone who disagrees with your new opinion is a bad person.” That statement coupled with your failure to address my very real concerns about supplements and the supplement industry leads me to wonder if you are trying to marginalize me so that people will be distracted from the facts I’m presenting about a very dirty industry.

You said, “mentioning a person’s ad hominem attacks is not an ad hominem attack. (You can find the phrase in your dictionary.)”

If I thought you were an MD, I’d tell you that sounds quite arrogant to me which I guess shows I have a double standard, one for MDs and one for everyone else, at least when it comes to courtesy. I am not anywhere near as well educated as the majority of the people on this list. Neither do I have their facility with language. However, I could very easily engage in a logical debate with you if I chose. My major was philosophy. But I have no intention of debating, which in the supplement industry is extensively used as a marketing tool, a way to draw attention to the products, give the public the impression that “the experts disagree” and distract attention from the fact that supplement promoters aren’t presenting any evidence to substantiate their claims.

Thanks for the response. My issue with quality testing of supplements and phytomedicines is this. If the supplement has enough pharmacologic activity to treat a disease, the way a conventional drug would, why should we be less concerned about its quality, potency, purity, etc., than we should with a drug?

Is it the mere fact that it’s a supplement or a botanical? That seems illogical to me. Is it because the supplement has significant human use data and a reasonable amount of scientific evidence, as you say? If so, then shouldn’t a comparable drug be held to a similarly relaxed standard?

I don’t buy the argument about expense (and neither does FDA, typically). One should not be exempted from meeting agreed safety and efficacy standards simply because they cost money. We don’t let pharma sell things without controlled clinical trials, simply because they may cost $10-15K/patient. There needs to be a better justification than that to hold supplements to a lower standard. (Of course, some would say it’s justified because most supplements don’t actually do much. But in that case, such supplements shouldn’t be allowed to make efficacy claims.)

Also, re your comment:

It had been my understanding that identity testing for a single synthesized molecule was only actually required at the end of the process….

Most emphatically not. For an approved drug product, the manufacturer must at minimum perform a visual inspection and an identity test on every batch of active pharmaceutical ingredient before using it to make the final product. I believe the same holds true for any other ingredients that are considered ‘critical,’ even if they’re not ‘actives.’

Moreover, to accept an API based on appearance and ID as the only in-house tests, the manufacturer needs a certificate of analysis from the supplier, AND the manufacturer must have qualified the supplier’s processes and test methods. Qualification is intended to show that the supplier’s methods are reliable, i.e. that the manufacturer can trust them. Qualification typically requires that the manufacturer perform full testing on several API lots from the supplier (appearance, ID, overall purity, specific impurities, potency, etc.) to prove that the supplier’s test data are reliable. It also typically requires an on-site inspection of the supplier’s facilities, and a review of their documentation and quality assurance procedures. Finally, even with a qualified supplier, the manufacturer is expected to perform full testing on occasional lots of the API (I think at least once annually).

That’s for an approved drug. Requirements are relaxed somewhat for drugs in the early stages of development, simply because the necessary methods are often still in development as well.

Regarding the first point – we are down to semantic. Disease claims require FDA approval as if it were a drug – but anything can get this approval if they meet the requirements. The point is – it is not based upon substance but the claims made for them.

Also – isn’t this the point of my original blog post? We need to get away from this all-or-none system, because it leaves us with mostly no regulation of a broad spectrum of agents. There are lots of studies of herbs and supplements, but the FDA has nor process for reviewing them, and no bar for health claims except a full drug approval. If some evidence were required for all health claims then some of the billions of dollars from the supplement industry would go toward even more research. The system now is an incentive against research.

This is bad unless you ASSUME that many herbs and supplement have health benefits. I don’t. When they do get studies they tend to have little or no benefits, and hidden risks emerge. By having no regulation I think we are doing more harm than good.

I think that the Germans are doing fine with a system whereby botanicals are allowed to make health claims that are supported by significant human use data and a reasonable amount of scientific evidence. Germany does have stringent quality control regulations, but these have not been written to prevent phytomedicines from being marketed (and often prescribed and covered by insurance). Likewise, Canada allows traditional medicines to make qualified health claims as such (at least for diseases that the regulators deem appropriate for patient-directed treatment), and people have not been dying like flies from “dangerous supplements” up there. If the medical profession admitted that tomatoes might prevent prostate cancer, I would not take that as evidence that only standardized tomatoes should be sold, nor that tomatoes should be prescription-only. One of the advantages of traditional medicine is its lower cost; a botanical should not have regulations heaped on it that are more appropriate to a toxic drug, if the result will be that the botanical costs more than a drug but is not covered by insurance. Consumers want product quality, not regulations that deprive them of access to products.

If the drug maker must only do one set of chromatographic tests per batch, while the supplement maker must do two, then more costly requirements are being demanded of the latter.

In fact, the same rules do apply to drugs. You have to test the API and all other critical ingredients before making the batch, then you have to test the final product to prove that it’s what it should be. That includes not just purity & related quality tests, but also identity tests. In fact, of all the required tests, FDA treats identity tests at the beginning and end of manufacture as among the most important. This largely to avoid mix-ups, which do sometimes happen, and can have devastating consequences if not caught.

One can argue whether such testing is generally necessary, but in this instance at least, the supplement GMPs are not more stringent. (Whether DSHEA mandates they should be less stringent is beyond my knowledge.)

I do think that supplements should be less expensively regulated. How can we say that a product must be expensively controlled to maximize efficacy, when official policy says that it is not to be considered efficacious for any disease?

Fair enough, but should supplements be able to make efficacy claims, in your opinion? And if so, should they then be subject to regulatory controls similar to drugs? Let’s ignore for the moment whether current drug GMPs are appropriate. I’m interested in whether you think supplements should be able to make claims like drugs, but still be held to a lower regulatory standard.

That’s what I was trying to get at originally. Sorry for being unclear (& thanks for the considered replies above).

This is incredibly random, but where has Pec been recently

Sadly for Steve Novella, he appears to have infested Steve’s personal blog.

Structure-function claims certainly are legally required to have scientific backing, and certainly ought to have. But if they were to be preapproved by a government agency, we need an agency more liberal in its attitude than the FDA. A “solid” study can’t mean one with negative results, and the amount of research required to support a claim can’t cost more than anyone could hope to recover selling the plant.

This contravenes DSHEA, which told the FDA to produce foodlike GMPs. (Food manufacturers do not have to do so many tests. As another example: If a lot of thyme, say, is divided up and sold to 100 supplement manufacturers, each of the latter must independently reprove its identity, without relying on certificates of analysis. But if it is sent to Campbell’s to put in soup, they can just accept the supplier’s certificate of analysis.) I do think that supplements should be less expensively regulated. How can we say that a product must be expensively controlled to maximize efficacy, when official policy says that it is not to be considered efficacious for any disease? There is also a broader therapeutic dose range for surviving botanicals than for most drugs; tincture of echinacea is more comparable to prune juice, which will alleviate constipation to some degree even if it is less potent than average and will not kill you if it’s more potent than average, than to Tylenol, which might kill you if it’s not carefully standardized.

Rosemary – I’m sympathetic to the harm you’ve experienced from suffering argyrism. Silver supplements are not by my definition traditional medicine but weird quackery from the era of heavy-metal allopathy, and I’ve never had anything good to say about them. I certainly wish FTC would make an example of the people who market them with false claims to innocent folks like you. They have the legal authority to do so.

I hope your suffering will not lead you to believe that anyone who disagrees with your new opinion is a bad person. I did not “call Joe names”; mentioning a person’s ad hominem attacks is not an ad hominem attack. (You can find the phrase in your dictionary.) In fact, while some people in the industry (and some herbalists) legitimately disagreed with the FDA’s assessment of ephedra risk, many who did not use ephedra in their products supported or did not oppose the FDA ban. As for your “suspicions” that “somehow” I have a “personal interest” — to forestall you from stooping to ad hominem attacks, I will tell you exactly what my interest is. My family and I are satisfied users of botanicals, and I’ve seen them used by people in other countries who can afford only traditional medicine. I am pretty familiar with the scientific literature supporting the uses of, primarily, popular European herbs, which convinces me that our ancestors’ accumulated medical knowledge, though limited and imperfect, was not the less-than-zero some would suggest. However, I do not work in the supplement industry, however broadly defined, nor have any investment in it.

Steven Novella – It doesn’t make sense to say “supplements are not banned from making disease claims” when the making of a disease claim instantly moves the product from the supplement category to the drug category — thereby making it an illegal, unapproved, “misbranded” drug to be confiscated on the spot. As you note, it has recently become legally possible to pursue drug approval for botanicals, but approval is still almost impossible to achieve in practice. At least one company has run itself into the ground trying, with the result that others still think they are better off selling efficacious botanicals as supplements and counting on consumers to learn about their utility by word of mouth.

I do, however, think that if they are being promoted as having health benefits, even the broad structure-function claims, should be backed up with multiple solid studies, and no more “These statements have not been evaluated by the FDA…” disclaimers. If you can’t show that your product does something, then you shouldn’t be able to market it as doing anything.

This is not a intellectual game. It is about life and death, wellness and chronic disease. Like it or not we all learn through our senses and our experiences even Skeptics, scientists and academic MDs. Like it or not, the best antidote for an anticdote is an anticdote. When people tell me that a supplement known to be dangerous can’t possibly be because they have taken it for years and not been injured, I respond, “My mother smoked heavily for 65 years and never had lung cancer. Do you think that means that Camels are safe or that my mother was a very lucky lady?” (That anecdote is an illustration which hopefully gets intelligent consumers to realize that N=1 means nothing.)

I have spoken with many very frustrated and worried public health officials who say that DSHEA will be on the books till there is a major disaster. They say that historically it has always taken such an event to motivate the public to change such a horrible law.

Many years ago I corresponded with a pharmacognosist who held a high position with the FDA who contacted me after seeing my posts on the Health Fraud list. He was expecting such a disaster and hoped that no one he loved would be injured or killed. Then guess what, he was gone from FDA. I was told that he’d taken a job with a supplement company. Maybe he thinks he has a better chance of keeping dangerous supplements off the market there than at the FDA? I don’t have a clue.

The fiction that supplements are “food” means consumers are not provided full disclosure about the products. I would like consumers of supplements to have access to the kind of information I can get from the Natural Medicines Comprehensive Database (which requires subscription). At the very least, the products might carry a warning when they are known to interact with other medications.

When I get a prescription medication, it comes with an information sheet telling me more than I need to know. When I buy a bottle of over-the-counter Tylenol, it warns me not to take it with other products containing acetaminophen, and it lists all the inactive ingredients so I can make sure I’m not allergic to them. I was given a Chinese remedy called Lemonin that contained acetaminophen under the British name paracetamol, that contained no warnings, and that did not list the inactive ingredients at all. The person who was handing it out had no idea paracetamol was the same as Tylenol.

Apteryx, I consider myself a very proud member of the “anti-supplement lobby”. My interest in supplements is very personal and somehow I think yours is too. You can find out all about me by clicking on my profile which will bring you to my webpage or just go directly from here: http://rosemaryjacobs.com

Now who are you? Is my suspicion correct? Do you also have a personal interest in supplements?

Joe’s statements about ephedra are accurate although just the tip of the iceberg. So I have to assume that when you responded, “Joe – Your instant resort to ad hominem attacks suggests that you have little fact-based argument to offer, so I will not bother to debate with you,” that you thought that by calling him names you would distract readers from the fact that you weren’t giving them any way to verify that what Joe said is inaccurate as you claim. If there is an honest supplement manufacturer and if he followed the ephedra debacle, he would have been ashamed and stood up to the industry he belonged to, but I haven’t heard of any supplement manufacturer doing that. Have you?

Judging from your previous post where you said, “There are scam products being marketed with outrageous lies – almost entirely on the Internet, not by reputable manufacturers. Swindlers will always exist, and should be prosecuted. As far as I can tell, the FTC is not “unable to keep up”; they aren’t even trying,” I am going to guess that you will classify silver supplements in the scam category. If so, then why is it that the supplement industry protects the silver scammers and gives them a home in their thorny nest?

When the FDA published a proposed rule for silver supplements in the Federal Register (docket # 96N-0144) and requested comments, the supplement trade group, the Council for Irresponsible Nutrition, CNR, sent a letter stating, “In any further publication or communication on this topic, FDA should explicityly state that this rulemaking does not apply to dietary supplements.” Why do you think they wanted to protect the silver scammers and their right to sell dangerous, useless snake oil? Do you think their reason was based on science or on finance?

Please don’t tell me the good little scientists at CNR just weren’t aware of the scam that early in the game because I personally had already sat in a small room with members of the President’s Committee On Dietary Supplement Labels which included several supplement industry leaders, one of whom was Annette Dickinson, Ph.D, CNR’s Director of Scientific & Regulatory Affairs, and told them all about the scam. I even had a pile of documentation which included promotional material and the articles that the promotional material referenced which showed that the claims were fraudulent and I know very well that the industry saw it all.

Your remark about the FTC is flippant. I filed a complaint about silver quacks with that agency years ago. I found out how to do that by speaking with aides to one of my senators who put me in touch with a real live person at the FTC. When I told her on the phone that the salesmen were using quacks from the early 1900s as references, quacks they were pretending were contemporary scientists, she laughed and said, “They all do that.” I’m not sure of the # now without checking files, but I think she said that the FTC had 35 employees to deal with fraud in the entire US. And don’t blame Bush. Clinton was in the White House then.

And don’t tell me that there isn’t big money for small companies in supplements because I know of a few that made large sums in a short time. I also have a press release saying that Clifton Mining Company bought a controlling interest in ASAP, a Utah silver supplement company. Clifton said it was a “perfect fit”. It multiplied “silver values at least 50 fold”, not 50%, 50 fold! That’s some markup! Just think how much the mining companies could make if silver actually offered benefits and didn’t turn humans into smurfs!

If you regulate every industry in town but one, you don’t have to be a rocket scientist to know where the crooks will flock. The supplement industry is for all practical purposes unregulated and it is full of crooks and naive innocent people who believe salesmen’s claims without ever even realizing the need to verify them independently.

Rosemary Jacobs
Proud Member of the Anti-Supplement Lobby
Believer In Full Disclosure

I agree with many of your points that the current regulatory systems may actually inhibit clinical testing of supplements for disease indications. And I can also vouch for your figures on the per-patient costs of a typical clinical trial. (Although a year for IRB approval is pretty excessive, in my experience.)

I am, however, curious about a couple of things.

First, what makes you say the new GMPs for supplements are more stringent than drug GMPs? I know the drug GMPs reasonably well. So far, I’ve only skimmed the supplement GMPs, but they look pretty comparable.

Second, do you think the standards for quality, manufacturing controls, and efficacy data for supplements should be lower than for drugs? If so, why?