Topical Nerium oleander: “OK” , or “Unsafe at any Concentration”?

We are going to continue to discuss here the issue of science-based selection of active ingredients for skin care products, both from a safety and efficacy point of view. This is part of our mission to both educate consumers and to blow the whistle on an industry that is sadly rife with irrational inventions and a circle the wagons mentality when challenged on logical basics.  Note that the thrust of this post is about the use in skin care of  chemicals known to be cell toxins and poisons.

Our poster boy for this topic continues to be extracts of Nerium oleander, a well known poison, which is currently being marketed as the active ingredient in an anti-aging skin care product, promising numerous benefits to appearance. The product, Nerium AD, is widely marketed through a multilevel marketing scheme, to the tune of $100 million dollars last year, which at ~$100 per bottle suggests a million bottles were sold last year, and probably twice that amount will be sold this year. That’s a lot of oleander extract being applied to a lot of human skin. Now, you would think that selling a product based on such a well known poison would cause concerns about safety. The same ingredient is used in anti-cancer drugs which are sold by Nerium Biotechnology, the parent company of the MLM, who have sought but not received approval by the FDA to market the drug in this country as an adjunctive treatment for some cancers.

There is extensive peer reviewed published scientific research demonstrating the effects of the extracted chemicals, known as oleandrins (found in all oleander species of plants), both on whole organisms, and at a cellular level. The effects are well established. These oleander extracts cause “massive oxidative stress”, reduce protein synthesis, and can promote cell death (apoptosis).  If absorbed into bloodstream, these same chemicals can have effects on the heart, including heart block, which can be fatal.

As is true with all drugs as well as naturally occurring poisons, dosage counts.  The bigger the dose, the bigger the risk of untoward effects.  Also the route of exposure is important.  The skin has a barrier that protects against absorption of drugs and poisons, but it is not perfect.  Generally speaking, less will be absorbed through skin in comparison to ingestion through the mouth. Although there are all sorts of caveats to be applied – since the skin’s barrier function is not perfect and may be compromised by anything from sunburns to allergic irritations to skin conditions or diseases.  And things we are encouraged to do by the beauty industry, like defoliation (cleansers, mechanical), peels, and the like which reduce the skin’s barrier function and thereby increase the likelihood  that unwanted chemicals gain entry into the body.

We don’t know the concentration of oleandrins in the active ingredient in the product Nerium AD.  But we are constantly being bombarded with marketing materials claiming it is completely safe.  One argument we have seen presented is that it is safe because  it is applied to skin, not ingested. Another is that even if absorbed, it would be in such tiny amounts that it would not affect the heart.

We have not thus far questioned the product on the basis of systemic toxicity, but we  have expressed concerns about what it does to skin itself when applied regularly. Given that there is ample published research from Nerium Biotechnology, including the work of Dr. Newman and others  that Nerium extracts cause “massive oxidative stress” and reduce protein synthesis, it would seem to be quite illogical that this same substance is somehow good for skin. Oxidative stress is not considered a good thing by any skin physiologist we know. It is what solar radiation does to the skin, and is commonly associated with aging, not anti-aging. While we have repeatedly asked for an explanation as to how these facts add up logically, we have never received an answer. We hear lately a new marketing pitch– that the active ingredient is an “antioxidant”. Which leads to the obvious question of how something can be both “massively” oxidant and antioxidant at the same time. We will delve into that more in a future post.

The first paper presented below suggests that Nerium oleander extracts indeed can indeed cause major inflammatory events in skin, validating our chief persistent concern. The second and third papers demonstrate that extracts of oleander can be absorbed through the skin and may do so in amounts sufficient to cause heart problems. To be fair, we want to point out that these published findings are not testing Nerium AD (whose dose of oleandrins remains unknown). We are not suggesting that the commercial skin cream will cause these same effects. We are merely making the point that any claims of non-absorption of oleander extracts through skin do not comport with the evidence shown here.

What we are trying to demonstrate is the faulty logic of deploying products with any amount of these substances. If we had some cogent explanation of how they might confirm benefits, we might look to a risk/benefit balance. But in the absence of any clear benefit, revealed in published scientific literature, any risk of chronic, insidious inflammation (the expected result of “massive oxidation” applied regularly)  seems entirely unwarranted in our opinion. 

Chemical burns caused by the shrub nerium oleander

From: Ann Burns Fire Disasters.. 2010 Sep 30;23(3):128-30.

chemical burn oleander both feet

The first paper comes from the plastic surgery unit of a French Moroccan hospital. It documents two cases of severe chemical burns resulting from the use of local (topical) application of Nerium oleander as a folk remedy for skin problems.  It is published in the Annals of Burns and Fire Disasters.  The article is in French but if you access it at Pubmed using a Chrome browser you can get Google to translate to English .

 

 

Here is that link:   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188260/ 

Here is the abstract.

Nerium Oleander is a shrub that grows naturally in the Mediterranean

chemical burn oleander both knees

regions. In Morocco it is found in wet places. It is famous for its risk of systemic toxicity in cases of poisoning because of the presence of two alkaloids, especially oleandrine. The literature describes cases of local use of leaves of this plant against scabies, haemorrhoids, and boils. We report two cases of chemical burns of different gravity due to Nerium Oleander. This should lead to more widely diffused information for the general population and strict regulation of its marketing.
 

The photographs speak for themselves.

Cutaneous absorption of Oleander: Fact or fiction

From: J Emerg Trauma Shock. 2009 Jan-Apr; 2(1): 43–45.

The second paper demonstrates that the topical application of oleander plant extracts may result in cardiac poisoning. The doses received are probably considerably higher than if the skin had been normal (intact skin). It seems from the literature that only a few leaves are required to achieve toxic blood levels. Yellow oleander and Nerium oleander both contain the same “poisons” – cardiac glycosides – responsible for the toxicity of this family of plants. Here is the abstract and a link to the paper on PubMed:

Cardiac conduction disorders following oral ingestion of Oleander plant materials were documented earlier. Transcutaneous absorption of yellow oleander (Thevetia peruviana) leaf extract applied over non intact skin (raw wound) resulting in reversible cardiac conduction disorder observed in four healthy males who were free from any other systemic or electrolyte or metabolic disorders or exposure to pesticide or toxins is reported for the first time. Their hematological, biochemical, clinical, and echocardiogram status were within normal limits and free of any abnormalities. One among the four, presented for weakness and breathlessness (class II). He had bradycardia with Mobitz II block and hypotension without any other demonstrable localizing signs. The other three were identified in the community and without any symptoms. However, their ECG revealed bradycardia with Mobitz I block in two and complete heart block in the other. All of the four recovered well without any untoward events. Hence, it is suggested that physicians and practitioners have to elicit history and route of administration of unconventional therapy, whenever they are confronted with clinical challenges and during medical emergencies before embarking final decision.
 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700576/
 

Here is a third publication (abstract below) – reporting a single case of heart block requiring a pacemaker after use of a Nerium oleander extract.

Pacing Clin Electrophysiol. 2004 Dec;27(12):1686-8.

A rare cause of complete heart block after transdermal botanical treatment for psoriasis.

We report the case of a 59-year-old man with a new 3 degrees AV block with a history of psoriasis. After implantation of a definitive DDDR pacemaker, the patient reported a transdermal self-medication with an extract of Nerium oleander for the treatment of his psoriasis. The pharmacological, epidemiological, and clinical features are discussed in brief.

Here is the link:  http://www.ncbi.nlm.nih.gov/pubmed/15613134

In Summary

These scientific papers would seem to support our postulate that Nerium oleander extracts when applied regularly  could result in inflammatory damage to skin.  While we suspect the dosages of cardiac glycosides in the Nerium oleander extracts in these papers are higher than those obtained with products on the market, we continue to question why a substance known to cause oxidative stress (the precursor to inflammation) can be somehow good for the skin in the long run. At any dose.

Further, there is support for another contention from the latter two papers –  that cardiac glycosides in topically applied oleander extracts may be absorbed in quantities sufficient to cause life threatening heart toxicity – at least when applied to skin that has problems.  Again, we don’t address the issue of dosing, and there is no publication that informs us as to the amount of these poisons in Nerium AD or the amount in a typical folk medicine homemade poultice of Nerium leaves.  But it does definitely put to rest the claims we have heard that such toxins cannot penetrate into the body. Clearly, under some circumstances, they are absorbed, and can cause systemic toxicity.

And again, this literature informs us about extracts of oleander plants, not the product Nerium AD per se, even though it is widely marketed as containing extracts of Nerium oleander as its principal ingredient.  Additional materials (such as a much touted patent for the extraction method) make it clear that maximizing the concentration of cardiac glycosides is the goal of the processing of the nerium oleander leaves.

We make no statements of fact about the toxicity of Nerium AD, and we have not tested it as such. We do offer valid scientific concerns and encourage open scientific debate on the general topic of cardiac glycosides as active ingredients in anti-aging skin care. We do not claim to have a corner on the truth.  Rather, we seek answers to these important questions. We invite discussion and publish opposing viewpoints. Any scientists out there wish to chime in?

We here at BFT can well  identify with Ralph Nader - a whistleblower from an earlier generation – we thought we might tip our hats to him by recalling his seminal book:  Unsafe at Any Speed: The Designed-In Dangers of the American Automobile

As a hat tip to Mr. Nader we thought of a book title appropriate to our whistleblowing mission: Unsafe at Any Concentration: The Designed-In Dangers of Poisons in Skin Care Products

8 Comments

  1. RE says:

    I have a document obtained by a freedom of information act request to the Texas Attorney General’s office that you would find interesting regarding Nerium. You may obtain it yourself by sending a request the office of Attorney General of Texas Greg Abbott or I can scan it and email to you. Their turn around time is pretty quick, I only waited a few weeks and my request was sent 6 months ago. There may be even more info now if you do your own request. I requested any information available on complaints about Nerium to the Consumer Protection Division.

    I suspect that there is minimal oleander in this – I don’t have a link, but in a video they put out a pediatrician claims a toddler can drink 400 bottles of this stuff and not get sick – so not much in it or this doc is insane. But Nerium is proud to point people to this recording.

    Another bit of interesting reading is found at the patent office – search under patent applications for Nerium.

    Have you seen the “clinical trial” reports? Google this file name… nsc4finalreport07172011v5.pdf

    Thanks for your work!

    • drjohn says:

      The clinical trial results are quite humble, so to speak. A 20-30% improvements in an anti-aging skin care trial is not particularly impressive. Please do scan and e-mail the document you mention to docs@barefacedtruth.com. We have seen marketing materials with pictures of immense fields of oleander in S.A. Some sources document that a single leaf is enough to kill a child (e.g. READ HERE, but many other professional level references). If correct, a single plant with 250 leaves would be enough oleandrin to make 100,000 bottles of Nerium AD (250 leaves x 400 bottles per leaf = “toxic dose). There is probably enough N. oleander growing in any 100 yards of southern California freeway to supply the whole world with this for decades, if that is the case. ? So, why the field of oleander? Wouldn’t that be deceptive? Sell the farm!

    • Sue says:

      Thanks for the link to the pdf. I noticed that the report states that the active ingredient was not “absorbed systemically” into the blood of any patients. What exactly does that mean. They did not say was not “absorbed” into the blood.

      Here is my question. These reputable people put their name, reputation, and careers on the line (http://www.youtube.com/embed/d1EIJARO4Vc). Are they doing it to make a buck? Have they been misled and as such are answering the wrong questions? Are they very smart men who happen to be gullible in this situation? Or do they have a point about the safety?

      I have yet to see anything from Nerium that explains “how” it works…. hmmmm….

      • drjohn says:

        I suggest you contact the scientists who appeared on the video and ask them yourself. We tried and got no reply, but maybe you will have better luck. Here are some questions you might ask:

        1. Did you receive payment or any recompense to appear on that video, or for anything else to do with Nerium?
        2. Is Nerium oleander extract (cardiac glycosides) a know poison or not?
        3. For any toxin or drug with no proven efficacy, what is the correct dose based on a risk/benefit ratio analysis?
        4. How do you respond to the three papers here showing the skin effects of Nerium oleander – is it safe on skin?
        5. How do you respond to the papers showing systemic absorption of topically applied Nerium oleander?
        6. How can a substance scientifically proven (by Dr. Newman) to cause massive oxidative stress be good for skin?

        Please share the answers if you get any. Seems to me if they really believed in the absolute safety of this stuff they would be willing to engage in a legitimate scientific debate on the subject. We stand ready to publish anything they say to answer these key questions. If there is evidence, and sound logic, we can be convinced.

  2. Timov Muiren says:

    I would like to thank the Docs for taking the time to disseminate valuable information to all of us… which also includes the portion of the population that chooses to continue suffering from self-induced leucotomies.

    That being said, my virgin post on this wondrous blog would like to reiterate to the Nerium International acolytes that science is an evolving process just like folklore… and that’s probably the only similarity. Oh yeah, and that breasts are functional and entertaining at the same time.

    Now, its hard to leave any room for disagreement that Nerium oleander, oleandrin, etc is a cytotoxin, causes oxidative stress, etc. and the purported scientific validity of the Nerium AD cream is seriously lacking in “real” research methodology that provides statistically significant results or validity to the claims of anti-oxidant properties, anti-aging, and the next best thing since castor oil. (or pumpkin pie whichever you prefer)

    Anyone with a half a brain and one working hand could spend a few hours doing due diligence and find plenty of information which massively contradicts the religious claims of the Nerium skin cream product. I know this for a fact because I am 86.5% positive my father was a rabid orangutan. So you other two-leggers have no excuse to play make believe and pretend that reality isn’t reality in your constructed universe.

    Now for the good stuff… I would like to hear the good Doctors’ feedback and opinions on a few things. Something of note that struck me (like Daddy used to when I asked him if I could have the last banana in the bunch) in one of the studies of Nerium Oleander, specifically with Anvirzel and Oleandrin was an interesting finding in loss of telomere length, TRF2 reduction and triggered DNA damage induced signals resulting in cell arrest or apoptosis. Now I am not a biology nut by any means (just a plain nut) but the red flags started going off when I came across (drum roll please) telomere length.

    For the rest of us “Uninitiated to the League of Cell-Flows” (speaking in Bane voice)… This is the process that causes aging….huh? What? What did you saaay? Yes. The Telomere is the area of your nucleotide sequences that protects the end of your chromosome from deterioration or fusion with neighboring chromosomes. This is why the research has been done to test its effects of “killing” cancer because cancer cells increase the telomeres and replicate out of control. But when you remove it from normal cells it induces (SURPRISE!)…. AGING. I don’t know about you, folks… but that seems like a pretty strange property for an “Anti-Aging” cream, wouldn’t you say?

    Anyway. What do I know? I still suck my thumbs and occasionally wet my bed. But I would like to hear what the Docs wanna opine about this. http://www.researchgate.net/publication/12322729_Anvirzel_an_extract_of_Nerium_oleander_induces_cell_death_in_human_but_not_murine_cancer_cells

    Once that has settled in, I am also curious about another study (Newman was again involved) which hypothesizes that Oleandrin suppresses NF-kB which may block inflammatory responses. What effect would a compound that induces apoptosis and inflammation while also blocking NF-kB and be potentially anti-inflammatory have on human tissues? I’m not sure if I am asking the right questions but I am sure greater minds will prevail. Could this be the link of an alleged anti-oxidant property within the Nerium skin cream? http://cancerres.aacrjournals.org/content/60/14/3838.long

    ….. oh yeah! Before I forget. Not that it really matters at this point in our education… but I would like to point it out anyway because it looks like some dang Europeans think we must be auditioning for the sequel to Idiocracy (Luke Wilson will return) after they concluded that cardiac glycosides induce cell death in human cells by inhibiting general protein synthesis. They scientifically deduce we are ‘tards for the ongoing clinical trials to test CGs as anti-cancer agents in humans.
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008292

    Again, I invite the good Doctors to bestow any wisdom they choose to impart upon us.

    Thanks again for all your hard work. It is very much appreciated.

  3. Frank C says:

    This is scary stuff but I have to say that I am a 47 year old man with very rashy skin especially in the winter. My mother bought into the pyramid thing with the company, which I refuse to do since I have a full time job in sales, I don’t need to sell my friends. The crazy thing is the stuff has made my face look good no way do I look younger one bit but the rashy face is gone. I have gone to dermatologists and used cortizone based medications and Nizoral (Ketoconazole) which never really worked. After reading the stuff on this site I am thinking about stopping using this stuff. Again it does nothing on aging for me but it definitely clears up my face. Do you think there is any long term effects I should be worried about.

    • drjohn says:

      Frank, We have written extensively about our concerns regarding cytotoxins applied chronically. Please read the related posts on the list. Rashy skin especially in the winter is highly suggestive of issues with hydration. Maybe the aloe is helping. You might consider trying a simple, inexpensive deep moisturizer.

  4. jon o says:

    So does the aging start when u stop taking it? Cus young guys who have been in the company for years look really aged lately.

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