Anti-inflammatory extracts and topicals - what works best?

ZinkZink Member
edited January 2 in Formulating
Before I dig into the literature, I'm wondering if any of you have any real world experience with anti-inflammatory extracts or their constituents, it seems that most brands use some combination of extracts (water/CO2/essential oil etc) either for label beautification and/or to make the products perform better.

A presumably functional example: Acne.org adding licorice root extract to their AHA moisturizer (18ß-Glycyrrhetinic Acid is stable at low pH).

A lot of my customers have acne, so in theory it could make a lot of sense to add mild anti-inflammatory ingredients to our general use moisturizer.
  1. What extract gives the most bang for your buck with high general tolerability? There are a ton to choose from with widely varying constituents (licorice root, calendula, etc.)
  2. Are non-extract non-OTC drug ingredients likely better in terms of value and/or side effect profile?
  3. Are there any reasons besides cost that such ingredients (or anti-inflammatories in general) should NOT be used in one size fits all formulas? 

Comments

  • PerryPerry Administrator, Professional Chemist
    I have real world experience with extracts and the suppliers of extracts. Extracts are added for only one reason...to support the marketing story. They don't have any impact on the performance of the product.

    If you're looking to put an extract in your formula, expect it to have exactly zero impact on the performance of the product. Especially an anti-acne product.

    The stuff published in literature about extracts is not reliable and overly optimistic. There are a number of reasons for this including...

    A.  Publication bias - no one publishes the studies where they found no effect
    B.  Motivated researchers - most of the studies are published by people who want to find an effect.
    C.  Inconsistent supply - you're never able to buy exactly the same extract twice.
    D.  Questionable supply - you have no reliable way to identify the composition of an extract. Is it licorice extract or propylene glycol spiked with brown food coloring?

    To answer your questions...

    1.  No extract works reliably enough to base a formula on it.
    2.  No, non-OTC ingredients are not better & they don't work reliably.
    3.  No/yes - These are claims ingredients & they help convince people to buy your otherwise standard product.  But they can introduce unknown allergens and can actually cause problems with your product.

    The reality is that if there was an extract that was effective, researchers would figure out which ingredient in that extract was responsible for the effect. That ingredient would be isolated and then that's what would be recommended for use. Lots of the effective drugs we use today came from some plant extract. There is nothing special that the extract provides that a synthesized version of the active ingredient couldn't.
  • ZinkZink Member
    edited January 2
    Thanks for the detailed answer! Always healthy with a solid dose of skepticism when it comes to cosmeceuticals, but I think you may be too dismissive so not closing the thread for submissions just yet..

    Counterarguments:

    A.  Publication bias - no one publishes the studies where they found no effect
    Applies to all research and not entirely true, there are still studies published showing no or little effect.

    B.  Motivated researchers - most of the studies are published by people who want to find an effect.
    Applies to all research, but possibly less true with natural ingredients that can't easily be patented as there are less financial incentives.

    C & D.  Inconsistent/questionable supply - you're never able to buy exactly the same extract twice.
    Non issue with a lot of extracts, will a thyme essential oil not contain thymol? Will NOW foods sell you brown scented food coloring? Very unlikely and hard to fake due to the scent. AFAIK the variability of constituents of essential oils also isn't high enough to make any performance difference.

    With more sensitive and low concentration constituents the extraction method could be critical, and you would have to get HPLC data to verify that your extract contains what you're after both pre and post manufacture possibly for each batch.

    1.  No extract works reliably enough to base a formula on it.
    Bold claim that needs to be substantiated. It's a bit like saying no eastern medicine works because nothing has gone through phase III trials.

    2.  No, non-OTC ingredients are not better & they don't work reliably.
    Generally this is true, but not necessarily always. Depends on the degree of reliability, it's not a black and white issue.

    3.  No/yes - These are claims ingredients & they help convince people to buy your otherwise standard product.  But they can introduce unknown allergens and can actually cause problems with your product.
    Definitely important to look at sensitization data if including something, yet not all extracts are made equal and some have very good tolerability profiles AFAIK.

    (4). The reality is that if there was an extract that was effective, researchers would figure out which ingredient in that extract was responsible for the effect. That ingredient would be isolated and then that's what would be recommended for use. Lots of the effective drugs we use today came from some plant extract. There is nothing special that the extract provides that a synthesized version of the active ingredient couldn't.

    Definitely, most of our drugs historically came from natural compounds, and researchers are isolating ingredients to see if they are effective and there is some evidence that they are (often fraught with methodological issues unfortunately, so it is indeed hard to draw solid conclusions).

    They are also recommended for use and sold (sometimes with hplc data) by reputable suppliers, but there is a huge $ gap from that to getting them approved for treatment of diseases as an OTC or rx drug (we see a similar trend in supplements, companies making improved forms of e.g. curcumin to increase bioavailability or BBB penetration etc). Even getting studies done by third parties is expensive and difficult to do right (btw, only one such study showing any significant effect is all the EU needs for you to sell something as treatment!).

    I'm however not set on using extracts vs purified or synthesized constituents of extracts.

  • It's not an extract but I read in some dermatology book that alpha-bisabolol shows promising results when it comes to anti-irritation. I can't recall which book it was but they induced inflammation using 24 hours SLS patch and then compared the speed of healing using the vehicle with and without bisabolol (at different %). Looks like it worked at just 0.15% pretty well. By works, I mean that redness got better several hours faster where bisabolol was applied. At least placebo controlled.
  • PerryPerry Administrator, Professional Chemist
    Certainly, it's possible that I'm too dismissive of cosmeceutical claims. I tend to have a more critical view of all things because I would rather err on the side of disbelieving something that is true over believing something that is false.

    Also, my response wasn't meant to close any discussion. I'm happy to read / discuss where I might be wrong.

    Comments...

    A. Publication bias - "Applies to all research and not entirely true, there are still studies published showing no or little effect."  - I agree it happens in all subjects. That doesn't make it any less of a problem in cosmetic science. I think it is more of a problem in cosmetic science however because there is a lot less publicly funded / independent research. Papers published related to cosmetic treatments are often done by researchers who's companies benefit from positive press.

    B.  Motivated researchers - "...but possibly less true with natural ingredients that can't easily be patented as there are less financial incentives." - There are numerous researchers who have a "natural" bias and take on subjects to prove nature is superior to what other researchers can invent. Also, there are huge brands built on the notion that natural is better and they benefit financially from propagating that myth. Getting patents in cosmetics is not nearly as useful as getting good press. Brands sell cosmetic products, not technology or even performance.

    C & D.  Supply - It's much easier to doctor natural ingredients than you know. People still sell and buy grapefruit seed extract as a preservative, even though it's been fairly well demonstrated to only work because it is spiked with parabens. You may have more faith in the sincerity of suppliers than I do. I've just seen a lot of shenanigans that go on in the cosmetic industry.

    1. No extract works reliably enough to base a formula on it. "Bold claim that needs to be substantiated." - A bold claim perhaps, but it is not one that needs to be substantiated. No one can "prove" a negative claim. But you could dispute the claim by showing a product that uses only an extract as its main ingredient and the results from that. AFAIK there is no such product. 

    I would say no "eastern medicine" that hasn't been proven by a double-blind study works. Similarly, no "western medicine" that hasn't been proven by a double-blind study works either. There is no such thing as "alternative medicine."  There are just things that work, and things that don't.  Which eastern medicine "works" that hasn't been incorporated into working medicine?

    - I think supplements, at least in the US, are mostly a scam (except when prescribed by a doctor) and it is safer to avoid them than to use them. They are less regulated than cosmetics even though they are significantly more dangerous. 

    I do apologize that this has gone a bit off from the original question. I just haven't seen reliable data that would make me recommend an extract for use as an anti-inflammatory. If someone has data to the contrary, I'd be keen to review it.  
  • Perhaps it's good to take a look at the constituents, if we were to look at the trends, i believe Dipotassium Glycyrrhizate has been there for years, and on trend ingredients would probably be Centella Asiatica or it's constituents such as TECA (from Seppic; Asiaticoside (and) Madecassic Acid (and) Asiatic Acid) or Madecassoside. 
  • EVchemEVchem Member
    I count bisabolol as an extract, you can buy natural bisabolol sourced from the Brazilian Candeia tree. (I really like that molecule, there's tons of interesting reading on it, not just to calm inflammation). 

    I think Perry and Zink both have good points. From a skeptical point of view, I'd believe most suppliers are selling glycerin and water that once touched a plant leaf for a brief moment. Companies that offer standardized extracts I have a more optimistic view of, but it comes down to how much people are willing to pay. 

     In the words of Tim Minchin, 
    "You know what they call alternative medicine that's been proved to work? - Medicine.”

  • ngarayeva001ngarayeva001 Member
    edited January 3
    @EVchem, I would appreciate if you share some materials on bisabolol. I am usually sceptical but bisabolol sounds promising. I read about it in some dermatology book which I have been looking for since yesterday but can't find.
  • MarkBroussardMarkBroussard Member, Professional Chemist
    Most reputable suppliers sell extracts as either a 50%/50% mix of Glycerin/Water + 8% Extract.  If you are loading in 1% Extract blend, which is common, you're actually winding up with a miniscule amount of actual extract in the formula.

    As Perry mentioned, if you want an effective formula, look to add the individual compound derived from the extract that has proven to be effective.
    Chemist/Microbiologist formulating in the Organic & Naturals arena under ECOCert/Natural Products Assn/Whole Foods/National Organic Program guidelines focused skincare & haircare products. 

    See website for details www.desertinbloomcosmeticslab.com
  • You can look at OTC supplements
    MSM comes to mind
    https://en.wikipedia.org/wiki/Methylsulfonylmethane

    But you'd need to make sure they are non irritant when applied to the skin. There's a big difference between eating them and rubbing them on the skin.
  • EVchemEVchem Member
    @ngarayeva001

    Here are the two I could find on my computer easily, I'll search around for more. It's got use as a penetration enhancer, anti-inflammatory, skin lightener, and it's a terpene which I think are just a wild class of molecules. 
  • Thank you!
  • ZinkZink Member
    edited January 7
    C & D.  Supply - It's much easier to doctor natural ingredients than you know. People still sell and buy grapefruit seed extract as a preservative, even though it's been fairly well demonstrated to only work because it is spiked with parabens. You may have more faith in the sincerity of suppliers than I do. I've just seen a lot of shenanigans that go on in the cosmetic industry.

    Think e.g. Seppic or CLR-Berlin would risk their reputation by selling fake ingredients? I don't think so, especially with the ease of which you can do analysis now to verify that you're getting what you paid for.

    you could dispute the claim by showing a product that uses only an extract as its main ingredient and the results from that. AFAIK there is no such product. 

    Easy to prove you wrong here, look at any of the FDA approved OTC ingredients for various skin issues and then look for extracts that contain them, e.g. willow bark extract containing salicin which is metabolized to salicylic acid in the skin - you just need to make sure you're using enough to get effects, which would require HPLC analysis of the extract and/or using standardized ones by reputable suppliers.

    I would say no "eastern medicine" that hasn't been proven by a double-blind study works. Similarly, no "western medicine" that hasn't been proven by a double-blind study works either. There is no such thing as "alternative medicine."  There are just things that work, and things that don't.  Which eastern medicine "works" that hasn't been incorporated into working medicine?

    One example, Artemisinin contained in sweet wormwood which was used in eastern medicine for more than 2000 years to treat malaria, in 1969 an extract of the plant was found effective (using a similar cold extraction process recommended 340 BCE), later Arthemisinin was purified and sold as a drug. https://en.wikipedia.org/wiki/Artemisinin (naturally it's best to have a standardized drug, but that doesn't mean the herbal extracts didn't work).

    It's seems arrogant to say that no eastern medicine that hasn't been verified by our western standards has any effect, have we tested them all? No. Even double blinded placebo controlled trials are flawed and can loose signal in averages (if a treatment only works for people with a certain genetic makeup etc, creating false negatives), or can show statistically significant results with only weak effects with large enough n's.

    You can find more examples in 2011 "Evidence-based Medicine for Traditional Chinese Medicine: Exploring the Evidence from a Western Medicine Perspective".

    In Alzheimer's treatment some doctors have started prescribing standardized and increased bioavailability versions of Curcumin as adjuvants made by reputable companies such as Now or Jarrows (companies that have been tested by Consumerlabs several times and always sold what they say they do).

    I digress

    Looks like I have some reading to do, Bisabolol and Dipotassium Glycyrrhizate were already on my list, the big questions are how they compare, whether they can be sourced from reputable vendors and whether they're likely to have clinical effects at practical/affordable use levels.

    Honestly if you wanted to do this right you'd need to assay their effects in the final product in vivo.
  • PerryPerry Administrator, Professional Chemist
    @Zink - Thanks for your thoughtful response.
    "Think e.g. Seppic or CLR-Berlin would risk their reputation by selling fake ingredients? "
    No, I don't. But there are literally hundreds of small distributors and start ups offering plant extracts in the us. (here's a sampling - https://www.thomasnet.com/products/herbal-extracts-26821009-1.html) These companies do not all adhere to the same standards. They also know that most of their customers (small contract manufacturers) usually won't do testing beyond the CofA. It's too costly and most don't care.  Are you suggesting there are no unscrupulous suppliers?
    Easy to prove you wrong here...
    You have provided a theory which is interesting enough but you've not disputed the original claim. There are many reasons why an extract could contain a derivative of a known, effective ingredient but the extract isn't effective. Suppose for example, willow bark extract contains only 0.1% salicin but for a specific treatment you need 2% salicylic acid to be effective. You could formulate with 100% extract and still not get a working product. Additionally, the "effective" ingredient could be bound up with some other ingredient in the extract to make it less effective. There are lots of reasons why an extract may not be effective despite containing an effective ingredient.  

    But you didn't address the original claim made - "No extract works reliably enough to base a formula on it."  - Where is a successful product on the market that is based only on an extract as its functional ingredient? 

    Also, if you know salicylic acid is the functional ingredient why wouldn't you just use that in your formulation instead of an extract that contains a small amount of it? Using the ingredient directly gives you much more control as a formulator.
    Artemisinin contained in sweet wormwood which was used in eastern medicine for more than 2000 years to treat malaria,
    Your example proves the point I was making. There was a traditional remedy, it was tested, proven to work, and now it's just...medicine. There are lots of eastern traditional treatments that don't work (e.g. rhino horn). Only through proper testing can we discover what is actually effective. Wouldn't you agree?

    I also don't understand how double blind studies are "western" standards? It seems to me they are just science. The same kind of science done by people in Japan, Korea, China, Thailand, etc. What am I missing? 

    Thanks again for your comments. It's always helpful for me to get a different perspective on things. 
  • ZinkZink Member
    edited January 7
    Basically I'm making the argument that extracts CAN work, and refuting that they can NEVER work.

    C.  Inconsistent supply - you're never able to buy exactly the same extract twice.
    D.  Questionable supply - you have no reliable way to identify the composition of an extract. Is it licorice extract or propylene glycol spiked with brown food coloring?
    ...
    are you suggesting there are no unscrupulous suppliers?

    No I am sure you're right that there are, but you were making too strong negative claims, that you can NEVER buy the same extract twice or that there is NO way of identifying what it contains. A combination of using reputable vendors and per-batch analysis of the extracts will get around the issue of supply consistency. This also holds true for willow bark extract and it still holds that I disputed your claim, given that you know the amount of salicin you're getting. Extracts can work.

    Where is a successful product on the market that is based only on an extract as its functional ingredient?

    You can make a "successful product" with nothing than rebranded petrolatum, which wouldn't prove anything. One example of a good product that uses licorice root extract (+AHA) is acne.org's moisturizer, and they use enough to turn it pale yellow (if it's not food coloring ;).

    If you dig a bit you can find studies where extracts or purified components of them  were added to base formulas and tested against the base formula alone (amazing how often they fail to test against the same base! often likely due to manufacturers sponsoring the trials..), which is what I'll be doing next, then you'll want to find several such studies and see if they agree. 

    Also, if you know salicylic acid is the functional ingredient why wouldn't you just use that in your formulation instead of an extract that contains a small amount of it? Using the ingredient directly gives you much more control as a formulator.
    One major reason is if you don't want your formula to be an OTC or even Rx drug.

    Why use Chamomile essential oil (37% Bisabolol) vs purified Bisabolol? You might want to use Chamomile EO if there are other useful constituents you want to include in your product or if you want the scent profile, OR use pure Bisabolol if the scent profile of Chamomile EO is too strong at the dose you'd need to use. Then there are marketing and price considerations.

    Personally I just want whatever works.

    Only through proper testing can we discover what is actually effective. Wouldn't you agree?

    I agree that the western method of testing efficacy is the best method we have to date, and that there is a lot of eastern medicine that's not effective. There are however examples of eastern medicines that were effective, which was subsequently proven by western evidence standards and turned into drugs.

    I also don't understand how double blind studies are "western" standards? It seems to me they are just science. The same kind of science done by people in Japan, Korea, China, Thailand, etc. What am I missing? 

    They're western because we came up with them, now they're of course used all over the world and traditional eastern medicine is being either verified or debunked by what's our current best bet standard of truth. I'm not promoting traditional eastern medicine's standard of evidence.

    But there's no such thing as just science when it comes to testing compounds, I alluded to some of the problems with our standard of evidence (based medicine) in my last post, these will continue to evolve and hopefully reduce the incidence of false positive and negative results (pre-registration of studies is another interesting requirement we could see in the future).

    There's also not such a thing as just medicine, evidence based medicine considers evidence of different strength, it's not black and white:
    • Level I: Evidence obtained from at least one properly designed randomized controlled trial.
    • Level II-1: Evidence obtained from well-designed controlled trials without randomization.
    • Level II-2: Evidence obtained from well-designed cohort studies or case-control studies, preferably from more than one center or research group.
    • Level II-3: Evidence obtained from multiple time series designs with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.
    • Level III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.
    https://en.wikipedia.org/wiki/Evidence-based_medicine

    One hypothetical example of why Level III evidence should be considered: Treatments that one doctor found to work for his patients might work because they for example are all from Iceland, whereas RCT's that found no effect were done on people with a different genotype or some other demographic difference.
  • @Zink:
    If you want to try Dipotassium Glycyrrhizate, I could send you a small quantity of the acid. I stock pure Glycyrrhizic Acid. You can easily convert it to the dipotassium salt by titration with KOH. I tend to use a lot more of the yellow-brown 12% liquorice powder extract (in shampoo).
    Cosmetic Brand Creation. Concept to name to IMPI search to logo and brand registration. In-house graphic design inc. Pantone specs. Cosmetic label and box design & graphics.
  • I know one popular cosmetic ingredient that does work, don’t think you would call it an extract though! After I had my first baby her behind came out in a big red rash, normal I was told. So I slathered on a ZnO laden cream & guess what? No red bottom next day! It’s the only anti inflammatory I know that works, heals sores even on your face. Put it on at night & it’s a million times better than any of the expensive treatments. I have tried nsaids, herbs like Arnica etc. Actually the only other compound that works is Salicylate we call it dencorub! Which also contains menthol for the cooling effects?? 
    Thoughts?
    Dr. Catherine Pratt
    (B.Sc with HONS I , Ph.D Analytical/Organic Chem and Microbiology), Cosmetic Chemistry IPCS)
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