Journal publisher retracted a study claiming poison oak could cure itching. Well done.

None of these plants will cure itching. 

Today I want to tell a positive story, where a science journal did the right thing.

I’ve written a lot over the years about bad science. A particular gripe of mine is when bogus scientific results, sometimes fraudulent, sometimes just sloppy, manage to sneak into the peer-reviewed scientific literature. This happens all too often, especially as the number of papers published each year has grown. These bad papers are then used by fraudsters and charlatans (and sometimes by innocent people who just don’t have the expertise to understand) to “prove” an unscientific claim.

Fortunately, a growing number of journals–the better ones, in general–are showing more concern than in the past, and taking actions (sometimes) to retract papers, even over the objections of the authors.

Before I get to the good news, a reminder about the most notorious scientific paper in recent memory: Andrew Wakefield’s fraudulent study in The Lancet, published in 1998, which claimed to find a link between vaccines and autism. The Lancet, to its everlasting shame, failed to retract the article until 2010, despite an avalanche of evidence that began appearing in 2002. Ten of the original 13 authors even published their own “Retraction of an Interpretation” in 2004, but The Lancet still refused to retract unless all the authors agreed. Wakefield, who was already leading the anti-vaccine movement and is now adored by anti-vaxxers, refused.

That article has probably contributed indirectly to the deaths of thousands of people from vaccine-preventable infectious diseases. And given what we knew about it by 2002, The Lancet had no excuse for delaying retraction until 12 years after publication.

But I digress. Today I want to highlight an article whose retraction I called for a few years ago, one that the journal, Scientific Reports (published by Nature Publishing Group) did indeed retract, about 9 months later.

The paper I called out was a study that claimed that an extract of poison oak can be used to treat pain. If that sounds kind of ridiculous, that’s because it is. The actual paper sounded very science-y, as I pointed out in my original column. It was titled “Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS-mediated neuropathic pain in rats.”

Toxicodendron pubescens, in case you’re wondering, is poison oak. It’s not a tree and it has nothing to do with oaks–it’s a cousin of poison ivy, and both plants contain oils that can cause extreme itching and painful rashes on contact.

How on earth could poison oak be used to treat pain? Well, it can’t. The paper was actually about a homeopathic treatment. One of the core tenets of homeopathy is that “like cures like,” as long as you dilute it sufficiently. So the poison oak paper started with the premise that since poison oak causes pain and itching, you can also use it, after you dilute it, to treat pain and itching!

Homeopathy, as I’ve written before, is a highly implausible and easily disprovable set of beliefs about medicine. I use the word “belief” intentionally here, because homeopathy really has no claim to be a type of medicine, or even a hypothesis. It’s just a 200-year-old collection of beliefs that turned out, long ago, to be wrong.

If this sounds absurd, well, selling these products is a highly profitable business. For example, check out Boericke & Tafel’s Oral Ivy Liquid ($15 for a 1-ounce bottle on Amazon.com), a homeopathic product that is made from poison ivy, poison oak, and poison sumac. It claims to be “for the prevention and temporary relief of contact dermatitis associated with poison ivy, poison oak or poison sumac.” What’s in it? Poison oak, at very low levels. (Actually this product isn’t really diluted to homeopathic levels: the packaging says it contains 0.02g of poison oak in each drop. So it might actually cause an allergic reaction–I’d stay far away from this stuff.)

Back to the study: in the paper, the authors diluted a preparation of poison oak down to levels as low as 10-30, a common practice in homeopathy. The problem is, at that level of dilution, not even a single molecule of the original substance would remain. There’s simply no possibility that such a dilution could have any therapeutic benefit, but somehow they found an effect. Hmm.

A number of scientists wrote to the journal complaining that this result was extremely implausible, and that the experiments didn’t support the conclusions. To their credit, the journal editors took the complaints seriously and investigated. The retraction notice (read it here) pointed out another major problem as well: some of the figures were duplicates! Each figure is supposed to represent a different experiment, so duplication is a big problem, added to the fundamental implausibility of the study.

As is often the case when fraud is detected, the authors did not agree with the retraction.

When I wrote my column complaining about this study, I said the “the right thing to do would be to retract this paper, because its results are simply not valid. We'll see if that happens.” Well, about 9 months later, that’s exactly what happened.

A few years ago, I was in direct contact with the Editors-in-Chief at both Scientific Reports and PLoS ONE (about different papers than the one I’m discussing above), and they expressed genuine concern about fraudulent research, as well as a determination to do better at rooting it out. When journals do the right thing, we should applaud them. So here’s to Scientific Reports, who got it right this time.

Allergy sufferers beware! These eyedrops are a scam.

Spring allergy season is upon us, and plants are bursting into leaf and bloom, spreading pollen everywhere. For some of us, this otherwise beautiful season is a time to stock up on antihistamines and tissues, and we try our best to stay indoors.

When pollen causes red, itchy eyes, we look for eyedrops to provide some relief. The American Academy of Allergy, Asthma, and Immunology and has a list of eyedrops here that includes products such as Zaditor®, Alaway®, and others. These eyedrops contain real medicine that can soothe itchy eyes and reduce your allergy symptoms.

So I was in the pharmacy section of my local grocery store, Giant, looking for eye relief, but they were sold out of Zaditor. Right next to the empty slot, though, I saw a row of other eyedrops from a company called Similisan®, and I took the picture shown here.

Homeopathic eye drops at Giant Foods in Baltimore.

Looks legitimate, right? Each box has a cross on it (apparently intended to resemble the logo of the Red Cross), and they are in the pharmacy section. I picked up the box labeled "Allergy Eye Relief" to take a closer look, though, and saw the word "homeopathic" near the bottom of the box.

Uh oh. It turns out that these products are little more than very, very expensive bottles of sterile water. For $9.99 you get 10 ml of water that contains several extracts–in vanishingly small amounts–for which there is no evidence whatsoever that they have any effect on allergies. Similisan's allergy relief bottle contains:

• Honeybee
• Eyebright (a plant)
• Sabadilla lily (another plant)

Yes, that's right: they grind up honeybees and put them in the eyedrops. The (wacky) idea is that because bee stings cause allergic reactions, a tiny bit of ground-up bee in solution will prevent those reactions. This flawed principle is the basis for all of homeopathy, which has stuck around for 200 years despite the complete absence of evidence that it works.

As I've written before, homeopathic drugs get a free pass on regulation, thanks to Congress. Homeopaths will tell you that their drugs are regulated by the FDA (they often make this claim in the comments on my articles - just watch), but they're not. All the FDA can do is check to see if the products contain the ingredients listed on the label. Unlike real drugs, though, the FDA does not and cannot require that these "drugs" have any effect whatsoever.

I don't think I need to say more about ground-up bees, but what about those other two ingredients? Eyebright is a plant that has "little or no evidence of efficacy" for eye infections. Its use dates back to the ancient Greeks, and has an interesting history:

"Eyebright was used as early as Theophrastus and Dioscorides, who prescribed infusions for topical application in the treatment of eye infections. This in large part was due to the similarity of the “bloodshot” petals to irritated eyes."

That's right: the flower petals look like irritated eyes, and this was enough to get the early Greeks to try them out as a treatment. Needless to say, the physical appearance of a plant has nothing to do with its efficacy as a medicine. (But try telling that to a homeopath.)

Sabadilla, the third ingredient, is a plant extract used as an insecticide, with an active ingredient called veratrine. As Laura Pottorff from Colorado State University explains, "its dust can be highly irritating to the eyes." Therein lies the homeopath's motivation for using sabadilla in eyedrops: homeopaths believe that a substance that irritates the eyes will somehow soothe the eyes if it is sufficiently diluted.

Similisan claims that their 3 homeopathic eyedrops will relieve itching, burning, watering, and redness in your eyes. The box just says it's "manufactured according to homeopathic principles," but doesn't explain that it hasn't been shown to be effective. You have to go to their website to discover that

"The uses of our products are in compliance with official Homeopathic Compendia. They were not the subject of approved applications reviewed by the Food and Drug Administration prior to marketing." 

In other words, they've never presented any evidence that these things actually work.

One can only hope that the sabadilla in Similisan's eye drops is sufficiently diluted; if not, you're putting insecticide in your eyes. The package says that all three ingredients are at 6X dilution, which in homeopathic jargon means 1 part in 1 million. The problem is that homeopathic substances have no real standards, so we don't know how much of the active ingredients were in the original mixture before dilution.

I was curious to see if Whole Foods Market sold the same stuff, and not surprisingly they do, in their special section devoted to homeopathy. (I've written about WFM and their love affair with homeopathy before.) The only difference is that Similisan costs more at Whole Foods, $11.99 to $14.99 depending on which flavor you buy (check out the photo below).

Homeopathic eye drops at Whole Foods Market. How much

money do you want to waste on a tiny water bottle?

Homeopathic eye drops are nothing more than really, really expensive water. At $10 for 10 ml, that works out to $1000 per liter. Similisan proudly states that it's sold at a wide variety of U.S. retailers and pharmacies, including CVS, Kroger, Publix, RiteAid, Safeway, Target, Walgreens, Walmart, and Wegmans. Seems like they're doing quite a good business selling their $1000/liter water.

Consumers beware: the eyedrops you're looking at, even in the Pharmacy section of the store, might be expensive, ineffective make-believe medicine. Make sure to read the package closely; the fake medicine is sometimes right next to the real stuff, and the packaging is designed to fool you.

Zinc still doesn't work very well for colds

Cold cure manufacturers continue to push zinc as a cure, despite the lack of evidence.  Today, the Washington Post reported, not for the first time, that taking zinc will shorten the duration a cold by three days in adults.  Sounds pretty good!  Only it's wrong.

The Post reporter apparently didn't really get past the abstract for the new study, which isn't actually a study at all, but just a review of 17 other studies.  The review appeared on May 8 in the Canadian Medical Association Journal.

ALL of the studies were funded by the companies that make zinc supplements, mostly large pharmaceutical companies.  (Big Pharma or Big Supp, they are often the same companies.)  Here's a partial list of the sponsors: Warner Lambert, McNeil Consumer Products, Weider Nutrition, Truett Laboratories, Bristol Myers, Berko Ilac, and Quigley.  Not that there's anything wrong with that!

One problem with the Washington Post summary is that the benefit wasn't really three days, even if you believe the results.  Although the study looked at 17 trials, the core analysis only used eight of them, all of which used patients with naturally acquired colds.  The average benefit was 1.6 days, not 3 days, and it was highly variable.  Reuters and Fox reported the story more accurately as "one and a half days" and pointed out that the effect was just over two and a half days in adults.

Somehow, though, the benefit disappeared in children.  Could this be because children don't care so much about telling the investigators what they want to hear?

And what about those trials that didn't use naturally occurring colds.  As I pointed out in a recent blog post, if you look at only the studies where the researchers intentionally gave people a cold, the effect vanishes.

"The more rigorously scientific studies, where you took a group of people and gave half of them zinc and half a placebo and inoculated their nose with a cold virus, found there were no differences," said Terence Davidson, director of the UC San Diego Nasal Dysfunction Clinic in a February interview.

None of this stops ProPhase (NasdaqGM: PRPH), maker of ColdEeze zinc products, from making this claim on their website:

"Cold-EEZE® has been clinically proven to shorten the duration of the common cold by nearly half."  

As evidence, their website points to three studies from 10-20 years ago.  They conveniently ignore the more recent studies that showed far less (possibly no) benefit.

The authors of the latest review article graded the quality of evidence for five different outcomes.  Their report card on these studies has one "Moderate" and four "Low" grades.  Moderate means "further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Most of the grades were "low," which means

"further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate."  

So the authors themselves don't really trust their own study!  In the end, they conclude that "there is only a weak rationale" to recommend zinc.  And previous studies, not funded by supplement manufacturers, showed no benefit.  Who are you going to believe?

Save your money and use it to buy chicken soup instead.*

*The author receives no financial backing from the makers of chicken soup, although he does like it and would appreciate a free sample.

Got cold. Try zinc?

Having a cold is no fun.  Sore throat, runny nose, general feeling of all-around blechiness.  About the only good thing I can say about colds is that they don't last long, usually about a week.

We still don't have a cure for the common cold, but it's not for lack of trying.  For decades, Nobel laureate Linus Pauling promoted mega-doses of vitamin C as a way to prevent colds, but he turned out to be wrong on that one.  Somewhere in the neighborhood of 200 different viruses cause us to get colds, and we don't seem to be able to get rid of any of them.

In recent years, the most popular new remedy is zinc, usually in the form of a lozenge.  The evidence for zinc's effectiveness is not entirely clear, but a review published just last month, which looked at 13 different studies, concluded that zinc seems to help, just a little bit.  All 13 studies were randomized controlled trials, the gold standard of research, and collectively they included 966 people.

That sounds encouraging, but the benefit was disappointingly small: zinc seemed to shorten the duration of a cold by about one day.  So instead of being sick for 7 days, you might be sick for 6 days.

Or maybe not: Dr. Terence Davidson from UC San Diego argues that if you look at just the more rigorous studies, the effect vanishes entirely.

Chunks of elemental zinc

Then there are the worrisome reports that Zicam, a zinc-based cold remedy, causes people to lose their sense of smell.  (This may not sound so terrible, but some people reported a permanent loss.  Imagine never being able to smell fresh-baked bread again.)  In 2009, these reports led the FDA to issue a warning advising consumers to stop using three particular Zicam products.  In addition to over 130 reports directly to the FDA, Zicam's manufacturer had over 800 additional complaints about loss of sense of smell.

In an ironic twist, Zicam markets its products as homeopathic remedies, which means that the FDA cannot regulate them. It also means that they shouldn't contain any active ingredients, because homeopathic preparations are diluted until they contain nothing at all.  But Zicam does contain zinc, quite a lot of it, and the FDA's warning letter demanded that Zicam stop marketing these products because they had never demonstrated that they were safe and effective.

Zicam markets a wide range of zinc-containing products, and the FDA's warning only affected three of them.  Zicam's website today states that "there is no valid, scientific evidence showing a link between Zicam and anosmia [loss of sense of smell]."  Strictly speaking, this is correct, but there have been published reports suggesting a link, such as this one from 2006 and this one from 2009.  These studies looked at nasal sprays, not lozenges, suggesting that the risk (if any) comes from spraying the zinc product directly up your nose.

Aside: Zicam also claims that their products cure allergies too, for which there is not a shred of evidence.  Their website makes the sweeping claim that "all Zicam products are both effective and safe when taken as directed." I see no reason to trust these guys.

Conclusion: I'm not taking zinc.  The side effects might be minimal, but the benefit is very small and possibly zero.  I'll stick with hot tea, which at least makes my throat feel better.  Or chicken soup.  That can cure almost anything.

Strychnine for your child's cold - courtesy of your friendly homeopath

I was in the pharmacy section of my local grocery store last week, looking for children's ibuprofen, when I stumbled upon Children's ColdCalm, a homeopathic product from Boiron.

This stuff isn't cheap - it's $12.49 at RiteAid, and the price is similar at my local grocery stores (Giant Foods and Whole Foods). If you follow the instructions, you'll give half the package (40 pills) to your child in the first 12 hours.

Not only is it expensive, but it doesn't work - or at least there's no evidence that it does. Boiron is selling parents sugar pills and telling them that it will cure their children of colds. Here's what the package says, right on the front: "Multi-Symptom Cold Relief, Sneezing, Runny Nose, Nasal Congestion, Minor Sore Throat."

Since it's in the "Colds" section of the pharmacy, most parents probably assume this is just like any other medicine. But it's not. It's a homeopathic drug.

The manufacturer, Boiron, makes very specifc claims on their website. Here's a partial list of ColdCalm's ingredients with their claimed benefits:

Belladonna 6C HPUS * Relieves colds with a sudden onset

Eupatorium perfoliatum 3C HPUS * Relieves sinus pain

Gelsemium sempervirens 6C HPUS * Relieves headaches associated with colds

Kali bichromicum 6C HPUS * Relieves nasal discharge

Nux vomica 3C HPUS * Relieves sneezing attacks

Phytolacca decandra 6C HPUS * Relieves sore throat associated with colds

Pulsatilla 6C HPUS * Relieves colds with a loss of taste and smell

What the heck are these? Belladonna sounds familiar - oh yes, that because it's an extremely toxic plant, also called Deadly Nightshade, one of the most poisonous plants in the Western hemisphere.

And "nux vomica": that sounds suspicious. Maybe that's because it is actually strychnine! Yes, that's right, strychnine, once used as rat poison, which is fatal to adults in doses as small as 30 milligrams. I wonder how much Boiron recommends that we give to children?

According to the American Cancer Society:

"Strychnos nux-vomica has not been proven effective for the treatment of any illness. Since the seeds contain strychnine, which is poisonous to humans, conventional medical practitioners do not recommend it as a medicine. Some research has shown that the level of poison in nux vomica preparations may depend greatly on how the seeds are processed."

Need I say more? Pulsutilla, another ingredient in ColdCalm, is a poisonous plant that produces toxins that slow the heart and can cause convulsions.

Is this how they want to cure my child's cold?

But wait, these are homeopathic medicines, which means they've been diluted down to nothing. So perhaps there's so little strychnine in the pills that it won't hurt your child, at least not too much. In ColdCalm, though, the dilutions aren't as tiny as the ones used in typical homeopathic preparations: 3C is one part in 1 million, so there might be some strychnine left in these tablets. We really don't know. A huge problem here is that none of these claims have been tested, so no one (including Boiron) knows what strychnine at these dilutions does to a child. Nor can they say precisely how much strychnine is in each tablet.

You might have noticed the abbreviation HPUS in that ingredient list: this refers to the Homeopathic Pharmacopoeia, a list of homeopathic drugs. HPUS drugs cannot be regulated by the FDA. Yes, you read that right. Homeopathic drugs are approved automatically as long as the homeopaths themselves list them in their "pharmacopoeia." No evidence of efficacy is required. We have Congress to thank for this - specifically, the Food, Drug and Cosmetics Act of 1938, which granted a special exception to homeopathic drugs. The Act was authored primarily by a Senator who believed in homeopathy.

I wrote about Boiron's ridiculous Oscillococcinum flu "cure" last year, but I didn't realize they have a whole line of bogus treatments for colds and flu. And Boiron isn't some small mom-and-pop operation: it's a huge multi-national company selling nothing but homeopathic products, making huge profits selling treatments that don't work.

So parents, if you see "homeopathic" on that package in the pharmacy, you might want to look a little harder at what they're selling you.