Arnica and a scientist’s frustrations

angry-1372523 - CopyWhen you’re the only scientist in the family you get asked the weirdest things. Actually, I’m not the only one, but the other one is a chemist and he’s mostly asked about astrophysics stuff, so he doesn’t really count, because I am the one who gets asked about rare diseases and medication side-effects and food advice. Never mind that I am a neuroscientist and I have professed repeatedly and quite loudly my minimum knowledge of everything from the neck down, all eyes turn to me when the new arthritis medication or the unexpected side-effects of that heart drug are being brought up. But, curiously, if I dare speak about brain stuff I get the looks that a thing the cat just dragged in gets. I guess everybody is an expert on how the brain works on account of having and using one, apparently. Everybody, but the actual neuroscience expert whose input on brain and behavior is to be tolerated and taken with a grain of salt at best, but whose opinion on stomach distress is of the utmost importance and must be listened to reverentially in utter silence [eyes roll].

So this is the background on which the following question was sprung on me: “Is arnica good for eczema?”. As always, being caught unawares by the sheer diversity of interests and afflictions my family and friends can have, I mumbled something about I don’t know what arnica is and said I will look it up.

This is an account of how I looked it up and what conclusions I arrived to or how a scientist tries to figure out something completely out of his or her field. First thing I did was to go on Wikipedia. Hold your horses, it was not about scientific information but for a first clarification step: is it a chemical, a drug, an insect, a plant maybe? I used to encourage my students to also use Wikipedia when they don’t have a clue what a word/concept/thing is. Kind of like a dictionary or a paper encyclopedia, if you will. To have a starting point. As a matter of fact Wikipedia is an online encyclopedia, right? Anyway, I found out that Arnica is a plant genus out of which one species, Arnica Montana, seems to be popular.

Then I went to the library. Luckily for me, the library can be accessed online from the comfort of my home and in my favorite pajamas in the incarnation of PubMed or Medline as it used to be affectionately called. It is the US National Library of Medicine maintained by the National Institutes of Health, a wonderful repository of scholarly papers (yeah, Google Scholar to PubMed is like the babbling of a two-year old to the Shakespearian sonnets; Google also has an agenda, which you won’t find on PubMed). Useful tip: when you look for a paper that is behind a paywall in Nature or Elsevier Journals or elsewhere, check the PubMed too because very few people seem to know that there is an obscure and incredibly helpful law saying that research paid by the US taxpayers should be available to the US taxpayer. A very sensible law passed only a few years ago that has the delightful effect of having FREE full text access to papers after a certain amount of months from publishing (look for the PMC icon in the upper right corner).

I searched for “arnica” and got almost 400 results. I sorted by “most recent”. The third hit was a review. I skimmed it and seemed to talk a lot about healing in homeopathy, at which point, naturally, I got a gloomy foreboding. But I persevered because one data point does not a trend make. Meaning that you need more than a paper – or a handful – to form an informed opinion. This line of thinking has been rewarded by the hit No. 14 in the search which had an interesting title in the sense that it was the first to hint to a mechanism through which this plant was having some effects. Mechanisms are important, they allow you to differentiate speculation from findings, so I always prefer papers that try to answer a “How?” question as opposed to the other kinds; whys are almost always speculative as they have a whiff of post factum rationalizations, whats are curious observations but, more often than not, a myriad factors can account for them, whens are an interesting hybrid between the whats and the hows – all interesting reads but for different purposes. Here is a hint: you want to publish in Nature or Science? Design an experiment that answers all the questions. Gone are the days when answering one question was enough to publish…

Digressions aside, the paper I am covering today sounds like a mechanism paper. Marzotto et al. (2016) cultured a particular line of human cells in a Petri dish destined to test the healing powers of Arnica montana. The experimental design seems simple enough: the control culture gets nothing and the experimental culture gets Arnica montana. Then, the authors check to see if there are differences in gene expressions between the two groups.

The authors applied different doses of Arnica montana to the cultures to see if the effects are dose-dependant. The doses used were… wait, bear with me, I’m not familiar with the system, it’s not metric. In the Methods, the authors say

Arnica m. was produced by Boiron Laboratoires (Lyon, France) according to the French Homeopathic pharmacopoeia and provided as a first centesimal dilution (Arnica m. 1c) of the hydroalcoholic extract (Mother Tincture, MT) in 30% ethanol/distilled water”.

Wait, what?! Centesimal… centesimal… wasn’t that the nothing-in-it scale from the pseudoscientific bull called homeopathy? Maybe I’m wrong, maybe there are some other uses for it and becomes clear later:

Arnica m. 1c was used to prepare the second centesimal dilution (Arnica m. 2c) by adding 50μl of 1c solution to 4.95ml of distilled ultra-pure water. Therefore, 2c corresponds to 10−4 of the MT”.

Holy Mother of God, this is worse than gibberish; this is voluntary misdirection, crap wrapped up in glitter, medieval tinkering sold as state-of-the-art 21st century science. Speaking of state-of-the-art, the authors submit their “doses” to a liquid chromatograph, a thin layer chromatograph, a double-beam spectrophotometer, a nanoparticle tracking analysis (?!) for what purposes I cannot fathom. On, no, I can: to sound science-y. To give credibility for the incredulous. To make money.

At which point I stopped reading the ridiculous nonsense and took a closer look at the authors and got hit with this:

“Competing Interests: The authors have declared that no competing interests exist. This study was funded by Boiron Laboratoires Lyon with a research agreement in partnership with University of Verona. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.”

No competing interests?? The biggest manufacturer of homeopathic crap in the world pays you to see if their product works and you have no competing interest? Maybe no other competing interests. There were some comments and replies to this paper after that, but it is all inconsequential because once you have faulty methods your results are irrelevant. Besides, the comments are from the same University, could be some internal feuding.

PLoS One, what have you done? You’re a peer-reviewed open access journal! What “peers” reviewed this paper and gave their ok for publication? Since when is homeopathy science?! What am I going to find that you publish next? Astrology? For shame… Give me that editor’s job because I am certain I can do better.

To wrap it up and tell you why I am so mad. The homeopathic scale system, that centesimal gibberish, is just that: gibberish. It is impossible to replicate this experiment without the product marketed by Boiron because nobody knows how much of the plant is in the dose, which parts of the plant, what kind of extract, or what concentration. So it’s like me handing you my special potion and telling you it makes warts disappear because it has parsley in it. But I don’t tell you my recipe, how much, if there anything else besides parsley in it, if I used the roots or only the leaves or anything. Now that, my friends, it’s not science, because science is REPLICABLE. Make no mistake: homeopathy is not science. Just like the rest of alternative medicine, homeopathy is a ruthless and dangerous business that is in sore need of lawmakers’ attention, like FDA or USDA. And for those who think this is a small paper, totally harmless, no impact, let me tell you that this paper had over 20,000 views (real science papers get hundreds, maybe thousands).

I would have oh so much more to rant on. But enough. Rant over.

Oh, not yet. Lastly, I checked a few other papers about arnica and my answer to the eczema question is: “It’s possible but no, I don’t think so. I don’t know really, I couldn’t find any serious study about it and I gave up looking after I found a lot of homeopathic red flags”. The answer I will give my family member? “Not the product you have, no. Go to the doctors, the ones with MDs after their name and do what they tell you. In addition, I, the one with a PhD after my name, will tell you this for free because you’re family: rub the contents of this bottle only once a day – no more! – on the affected area and you will start seeing improvements in three days. Do not use elsewhere, it’s quite potent!” Because placebo works and at least my water vial is poison free.

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Reference: Marzotto M, Bonafini C, Olioso D, Baruzzi A, Bettinetti L, Di Leva F, Galbiati E, & Bellavite P (10 Nov 2016). Arnica montana Stimulates Extracellular Matrix Gene Expression in a Macrophage Cell Line Differentiated to Wound-Healing Phenotype. PLoS One, 11(11):e0166340. PMID: 27832158, PMCID: PMC5104438, DOI: 10.1371/journal.pone.0166340. ABSTRACT | FREE FULLTEXT PDF 

By Neuronicus, 10 June 2017

EDIT [7 December 2022]: Look at that! There is a warning after the DOI that appeared on my website through no involvement of my own saying the paper has been retracted roughly 2 years after publication. Good! The official reason for retraction? They used nothing to find nothing, their “findings” are just “standard noise”. Told you so! PubPeer link here.

This is what PLoS One is saying about it (my highlights):

The PLOS ONE Editors have discussed the study design and results reported in this article with experts in RNA-seq analysis, statistical analysis and members of our Editorial Board. Based on our assessment and the advice received, and in light of the above concerns, we have determined that the results presented in this article do not provide sufficient support for claims about effects of Arnica m. on gene expression. Hence, we are retracting this article due to concerns about the study design and about the validity and reliability of the reported conclusions. We regret that these issues were not fully addressed during the article’s pre-publication peer review.
In addition to the above, the PLOS ONE Editors hereby notify readers that the Competing Interests statement was incorrect for this article and should have explicitly stated that Boiron Laboratories, a company that provided funding support for this study, markets homeopathic products including various dilutions of Arnica m.
MM, CB, DO, EG, and PB did not agree with retraction. AB, LB, and FDL did not respond.