This post arose from e-mail conversations with a gentleman representing a skin care company with an MLM model who impressed us because he was civil, knowledgeable, and willing to debate the science of his product. His name is Craig Peloquin and his company is Glissandra™ Skincare. Now, we have cursorily looked at the active ingredients, and have some issues on the scientific underpinnings. It basically relates to the theory of hormesis, which is a fancy way of saying a small amount of a thing that is bad for you is good for you. It is what homeopathic medicine relies upon. There is some truth to it, in some therapeutic paradigms, but we see it misapplied all the time. So we will be peppering their scientific advisor with questions once this gets fully underway. But to get things rolling, we are going to allow Craig to state the case for Glissandra’s technology. We will come back later with questions, as comments, which they have graciously agreed to answer.
I want to emphasize that this company scores points from the start just for showing up. Being willing to subject your work to scrutiny is what real science is all about. For this reason, we are going to suspend (at least temporarily) our bias that MLM is inherently evil. We are instead going to test the proposition that it is certain MLM’s that are evil, not the business model itself. In other words, our leap of faith is that an MLM can be a good thing. Having said that, we really are here to talk about science, not the business model. But if they can convince us that the science is sound, then they have taken the first large step in convincing us that a non-evil MLM is at least possible.
So, here is the opening gambit in the debate…
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Good day Dr. John, Dr. George, and all the BFT readers.
I thought we could start a new topic for your readers, as I indicated in a previous post I am a senior executive with an anti-aging skin care MLM company with 23 years of real science behind our products and we are more than happy to discuss the science behind our products as well as field any questions you and your readers may have.
I understand the bias in this blog for MLM companies, so let’s keep the business side out of this debate, since your blog is about science, let’s stick with the science.
Your readers will have their own opinion of MLM companies, of which obviously I am a strong proponent to this marketing concept. (bias acknowledged) 😉
I thought that the best way to start would be to open the topic with the Theories of Aging. This way we can look at all scientific approaches, not just the ones that we personally have an interest in.
Theories of Aging
Let me introduce my Chief Technology Officer, Prof. Robert Kam-Ming Ko. He is currently the Professor in the Division of Life Science at the Hong Kong University of Science & Technology. After graduating from the Chinese University of Hong Kong, he went on to Canada and obtained his Ph.D. in pharmacology at the University of British Columbia in 1990.
He then returned to Hong Kong to pursue his research work on Chinese herbal medicine. His research focuses on antioxidant and immunomodulatory properties in Chinese tonifying herbs in establishing their scientific basis in terms of modern medicine. He has edited three books and published more than 180 scientific papers and book chapters on related topics.
I trust that this information would be sufficient to qualify him as an expert in his field and he will be actively following our debate that will be copied on my blog at www.antiagingskincarescience.blogspot.com.
Let us start with the theories of aging.
Aging is a consequence of changes that are harmful, progressive, and thus far irreversible in most living organisms, including humans. Age-associated damage occurs to biomolecules, cells, and organs. Diseases such as arthritis, osteoporosis, heart diseases, cancer, Parkinson’s disease, and Alzheimer’s disease occur more frequently with old age.
The biochemical mechanism of aging has long been an area of intensive research, and a number of theories of aging have been proposed, including the neuro-endocrine theory, which links aging to hormonal changes; immunological theory, which attributes aging to immune system dysfunction; telomerase theory, which relates to the shortening of chromosomes during cell division; and oxidative stress theory, which refers to free radical damage to cells; stem cell exhaustion, which refers to the decline in the regenerative potential of tissues due to decreased number of stem cells, and the decline in their abilities to differentiate.
Among these theories, it is reasonable to distinguish those that attempt to establish primary causes of aging from those that are secondary. For example, the telomerase theory may be secondary since the decrease in telomerase activity can be caused by the increase in cellular oxidative stress.
In gerontology, the study of aging, oxidative stress is increasingly recognized as the primary cause of aging.
The role of mitochondrial decay in aging
If oxidative stress is indeed the primary factor in skin aging, it is important to understand its roots. Scientists now believe that oxidative stress may be caused by mitochondrial decay. Mitochondria, the chief producers of both energy and oxidants inside the cell, play a critical role in the process of aging.
As energy producers, mitochondria convert unusable forms of energy into a usable chemical form known as adenosine triphosphate (ATP), which is required for all vital cellular chemical reactions throughout the body. During the metabolic cycle of ATP production, oxidants are released from the mitochondria as harmful by-products that can damage important biomolecules, such as DNA, lipids, and proteins. At the same time, the mitochondria themselves are also victims of this metabolic cycle of ATP production as they are highly susceptible to damage by the oxidants thus released.
Over time, largely due to cumulated damage by the oxidants, the functional capabilities of mitochondria deteriorate; the production of ATP declines and the release of oxidants increases. The latter inflicts greater damage to the mitochondria, which in turn results in accelerated oxidant production. This is the vicious cycle of mitochondrial decay. If left unchecked, mitochondrial decay leads to cumulative damage in cellular biomolecules, resulting in a host of age-related diseases.
Effects of mitochondrial decay on the skin
The skin is the body’s largest organ. The consequence of cumulative damage in skin cell biomolecules is a corresponding increase in the depletion of important extracellular components, such as collagen, elastin, and hyaluronic acid, among others. The loss of these significant components is manifested in the appearance of wrinkles, fine lines, droopiness, pigmentation, puffiness, skin inelasticity, enlarged pores, dryness, and a dull skin tone.
Conclusion
An increasing amount of scientific evidence confirms that mitochondrial decay is the fundamental cause of aging; therefore, scientists are endeavoring to find remedies to reverse the declining functional capabilities of mitochondria due to aging.
More information on mitochondrial decay and theories of aging can be found at these independent websites:
National Institutes of Health (http://www.nih.gov)
PubMed (http://www.ncbi.nlm.nih.gov/pubmed)
Natural Standard (http://www.naturalstandard.com)
Craig Peloquin
Vice President of Sales and Marketing
Glissandra Skincare
Not to be picky, but I am compelled to gently point out that the Glissandra web site on its home page makes this claim:
“Glissandra™ is the first bioceutical skincare regimen proven to effectively reduce the visible signs of skin aging.”
Oh, really? It’s one thing to brag and say you are the best, but telling us that all the other products in the biologic category are ineffective and do nada for skin aging? Now you either need to prove that claim (no others are effective except yours) or confess to indulgence in marketing hype.
Dr. John,
I don’t see where we say that other products in the biologic category are ineffective and do nada for skin aging. If I read this correctly, it simply says Glissandra™ is the first. Come on Dr. John, no need to run when nobody is chasing you. We coined the term bioceutical in 2008 by combining biology and nutraceutical as a marketing term. I guess others liked the term and are using it now.
Craig
Some of us out here in “Cyberspace” were not born yesterday and realize that Tretinoin (Retin-A), was available far earlier than this Glissandra goop. And not to mention the fact that Retin-A has been proven to reduce the signs of aging with decades of real science.
Start with this post about vitamin A . Then if you are interested we can supply some advanced reading on the topic.
What have scientists found to fight the leading cause of skin aging – mitochondrial decay?
In our previous post, entitled “Theories of Aging”, we discussed how oxidative damage is regarded in the scientific community as the primary cause of aging, and how mitochondria play a significant role in this by being a major source of free radicals.
http://antiagingskincarescience.blogspot.ca/2014/06/theories-of-aging.html
Now, scientists have made a breakthrough in fighting the leading cause of skin aging: Schisandrins have been proven to effectively reverse mitochondrial decay.
http://www.ncbi.nlm.nih.gov/pubmed/19850987
A recap of our previous discussion
Mitochondrial decay in aging refers to a progressive disruption to mitochondrial
structural integrity and functional ability over time. Consequently, cells experience impaired energy production, a decline in normal function, and accelerated free radical generation. This is the phenomenon of cellular aging, which makes the cell more prone to apoptosis, or programmed cell death – much like cell suicide.
Skin aging – the signs of which are commonly manifested in wrinkles, fine lines, age spots, loss of suppleness, and deterioration of skin tone – has been proven to involve mitochondrial dysfunction.
The mitochondria–free radical connection
Research has shown that mitochondria are a major source of free radicals. Deteriorating mitochondria instigate a vicious cycle of exacerbated oxidative stress. Consistent with these findings is the concept that “manipulating the signaling pathways that regulate cellular antioxidant defense” and “controlling the intracellular levels of free radicals” is preferred over “altering individual antioxidant components by extrinsic supplementation”.
In simpler terms, this means that it may be more effective to combat aging by treating the source of free radical production rather than by “cleaning up” free radicals after they are generated. This theory is supported by recent studies that have found that scavenging free radicals through the supplementation of certain antioxidants could be ineffective or even harmful in the long run.i ii
iMortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention – Systematic Review and Meta-analysis, Bjelakovic et al; Journal of the American Medical Association 2007; 297(8):842-857 (doi:10.1001/jama.297.8.842).
iiVitamins in Aging, Health, and Longevity, David R Thomas; The Division of Geriatric Medicine, Saint Louis University Health Sciences Center, Saint Louis, MO, USA.
So far the discussion has centered on theories of aging, with which I have no particular bone to pick. But this is not the crux of the debate. Glissandra claims that it’s mechanism of action is related to hormesis, a construct that says simply “what doesn’t kill you you makes you stronger”. However, i would be quick to add “what doesn’t kill you quickly may lead to chronic inflammatory disorders and slow death”. It’s all about the timing, dosing, signaling, molecular interactions, etc. In other words, the devil is in the details.
Let me also say that I am a believer in hormesis and it’s therapeutic potential as a basic physiologic principle. The best known application may be exercise. It stresses physical systems, but they then recover and are stronger the next time challenged. Simple enough. But consider what would happen if you exercised all the time. I once had a patient who was obsessed with body fat and literally exercised herself to death. Exercise requires both a period of intense activity, and a period of recovery, to be beneficial. So, let me take a leap of logic and presume that this product causes a metabolic stress to the mitochondria of skin cells. But, it is not applied for an hour 3 times a week, it is applied twice daily, every day, assuming a constant rate of diffusion / absorption over that 12 hours from the cream. Toughens skin up (those cells that don’t die from the damage)? But wait – no recovery period. Won’t that just lead to chronic “cell danger response” signaling, and inflammation, with no down time to adapt? Maybe if the product sellers said to use it for a few days a month and then stop ….. at least that would match the paradigm.
Also, this theory it does not comport well with what we know about the skin in responding to chronic oxidative stress. The most salient example? UV stress. We experience it daily, chronically, and the damage to skin accumulates over time. Yes, we have adaptive responses (e.g. repairing DNA damage every night, kill off and replace the worst damaged cells, create more melanin as a filter to sunlight). But even sunlight is only for half the day. But the adaptations don’t completely compensate for the stresses. Over time, the the system deteriorates. Skin ages. Too much of this stress and it also gets cancer. As the theory goes, what doesn’t kill you may toughen you. Perhaps the flip side is true – what doesn’t toughen you may end up killing you.
I remain open to hormesis as a potentially beneficial mode of action for a dermal therapeutic, but would need to see specific evidence that ties a cyclical cellular stress to an adaptive (anti-inflammatory) response that is ultimately beneficial and does not lead to chronic inflammation and its consequences like disease, cancers, and aging itself.
All MLM’s are EVIL? How is that? Please explain this comment. As a person who actually uses Glissandra, and has seen results in a matter of 1 week, I don’t see how this company is evil. The company is more than willing to sell the products at a retail cost with no obligation. Have you done any research on how Glissandra can help reduce the signs of aging? Have you actually tried the products? I challenge you to put your money where your mouth is and actually try the product before you accuse Glissandra as being an EVIL company down to their core.
Rachel,
I appreciate your enthusiasm for our product and participating in this debate, however, this debate with BFT is designed to discuss the science behind Glissandra and not our MLM business model.
Just so the BFT readers can appreciate where you are coming from, I connected with Rachel only last month on LinkedIn because of her non-MLM company, Rubber Ducky Sunscreen. She was intrigued with the science behind our line, and even though Glissandra protects from ultra violet and infrared rays, we always suggest to double protect from the sun with a good sunscreen.
Rachel “put her money where her mouth is” and flew up to Vancouver, Canada on Thursday for a weekend Glissandra event. She wanted to meet Professor Ko who was our special guest. She did her homework. She researched our company and active ingredient. She did not come from an MLM background and wanted to learn more about the science and took the opportunity to meet our Founder and Head Scientist, who was just named the Associate Dean of Science at the Hong Kong University of Science and Technology.
So Ariel, I agree with Rachel in that you have made a very bold statement that our products are inherently suspect down to our evil core.
Then Dr. John, your reply doesn’t make sense either. How can a person benefit from our products without buying them? How would one of your readers benefit from Cellese without buying and trying the products?
I agree with the P.T. Barnum quote for companies without real science, not Glissandra.
The only way to make it risk free is to offer an unconditional, empty bottle, money back guarantee, which we do. We also offer a very inexpensive 5-day introductory set so a person can try it before they buy a full set of products. Oh, and 1 more thing, you don’t need to be part of our business plan to enjoy the benefits. You can become a customer and just purchase and use the products.
I know it is hard to understand because you and many of your readers have such a mistrust for MLM companies.
May I remind you that in your initial post we agreed to leave the MLM debate for another time and place.
Attention all Glissandra customers and distributors!
Please do not use this forum to market Glissandra. If you want to join the debate with product testimonials, please make sure you provide details as well as your own before and after photos, and I will post them on our blog at http://www.antiagingskincarescience.blogspot.com for everyone that is interested. This is NOT an opportunity seekers blog. Do that on a LinkedIn or Facebook group.
Respectfully, let’s all keep to the science.
You say this is all about science, but then you present us with nothing but marketing messages. The Rachel story (not the Biblical one!) is a marketing backgrounder, and adds nothing to the science debate. Your reiterating a money back guarantee is nothing but a marketing message. Your 5 day trial offer is nothing but a marketing message, and in fact confounds the science (a product based on hormesis or some other scientifically defensible physiologic mechanism with benefits in 5 days? I don’t think so). And,frankly, your repeated defending of MLM just causes some readers to want to disagree with you, and does nothing for the science. But notice – I am not the one who keeps bringing it up. Your bringing up Cellese (which is not a product) is odd as it is used to to justify the “you gotta try it” message – which to me is rather unscientific in its foundations because you induce trials or sales before you build a foundation for mechanism of action. Then you top it all off with another link to your selling website with invitations to send in before and after photos. Pure guerrilla marketing.
Frankly, this is not a scientific debate. I suspect you are a born marketer and just cannot help yourself. So let’s just skip all that and have Dr Ko show up and give us his scientific rational for how this product is supposed to work, and let him field all questions about the science. Forget the MLM stuff, forget about trying to sell on BFT.
Dr. John.
Agreed! The science, the whole science, and nothing but the science. Thank you!
Will believe it when I see it.
Dr. John,
Thank you for your thoughtful question.
Glissandra (ie schisandrin B) differs from other conventional hormetic agents in that it has a wide range of effective doses which are non-toxic to normal cells. Schisandrin B is chemically transformed in various cells by cytochrome P-450 enzymes and thus produces signalling reactive oxygen species (ROS) which do not cause pathogenic oxidative stress. Instead, the ROS will elicit a glutathione antioxidant response, particularly in mitochondria, which results in mitohormesis – a process that can be induced by blocking insulin signaling, dietary restriction and physical exercise, which are all shown to be effective to prolong a healthy lifespan. Schisandrin B work in the same way in skin cells. The safeguard of mitochondrial function and antioxidant defense is beneficial to retard the skin aging caused by intrinsic (ROS) and extrinsic factors (solar radiation).
I look forward to our continuing to share more science behind our Glissandra products line.
Robert
Welcome to the debate, it is a pleasure to have you here.
Now to start I need to explain to our readers that this discussion involves evolving theory in the realm of cell biology that even the average PhD would have difficulty understanding unless they are actively involved in researching these topics. Once we set the stage I will endeavor to focus in on what we call the translational research. Basic facts & hypotheses are translated to prototypes and products, and are tested for clinical utility in a way that affirms or dismisses the underlying theories. At the end of the day we realize that what interests most folks is insight into things that work, and why they work. Theory without tangible application interests scientists, not consumers.
The hyptotheses we are talking about here have to do with mitochondria, the energy factories present within cells of all types. It turns out the mitochondria are very important determinants of cell fate (cell death or survival from stress or injury), and thus are a center of focus for theories of aging. Now, it may be important to point out that whole organism aging and skin aging (or the appearance of same) at times may diverge, and thus manipulations of one don’t necessarily correlate with changes in the other. In simple human terms,living to 110 does not mean your skin will look young at 50. In some ways, the opposite may be true. So, we need to carefully dissect theories and experiments that have to do with theories of aging, mitochondrial energetics and ROS, tissue survival, etc, to make sure at the end of the day that the chain matches up.
As clinicians we often think backwards. Start with the problem and potential solution, then track backwards to find physiologic explanations that make sense. Let’s start with some basic questions for Dr. Ko from which we can work backwards.
1. What is the clinical evidence that Glissandra effects anti-aging benefits on skin? How are they documented?
2. How is the active delivered? What vehicle? In what doses? Continuous vs discontinuous? How deeply does it penetrate?
3. How is Glissandrin transported into cells to affect mitochondrial functions? By which known mechanism?
4. What cell populations in skin is it affecting?
5. If there is ROS signaling – what is the signal cascade? What other well known biochemicals are affected?
6. As with other mitochondrial stressors is there a shift toward anaerobic glycolysis?
Thanks in advance.
Dr. John, please find below my answers to your questions.
Respectfully, Robert
Hi Robert, thanks, our comments are presented interlinear fashion in bold type.
1. What is the clinical evidence that Glissandra effects anti-aging benefits on skin? How are they documented?
已經證明，以防止在體內和在體外通過太陽能光照射引起的氧化損害。
lol – okay even us scientists need to have a sense of humour!
We like humor at BFT. Hoping this doesn’t spell out some Chinese curses!
Seriously though, Glissandra has been shown to protect against oxidative damage induced by solar light irradiation both in vivo and in vitro.
That would qualify as antioxidant. Yet (based on what you have said) first it raises ROS (reactive oxygen species). Would you then say it is an a pro-oxidant first (ROS contributor) but then upon adaptation to repeated ROS stress (the signal) it becomes antioxidant (ROS quencher) with time?
Two clinical trials using Visual anti-aging assessments were conducted. The duration of the studies were 8 weeks. Data collected were tabulated and analyzed.
Visual trials with or without controls? Single arm studies without histology are extremely weak on the evidence scale. There are literally tens of thousands of such studies in the world of aesthetics, all generally saying the same thing. Are we to believe them all? It would help immensely to have some validation with split face, controls, serial histology, tape stripping for gene expressions or cytokines, etc.
North American Trial
Visual anti-aging assessments from 35 subjects of diverse ethnicities, with ages ranging from mid 20’s to late 60’s, from both genders.
Same question as above.
South East Asia Trial
Visual anti-aging assessments from 28 subjects of Asian ethnicity with 17 subjects with age <45, 8 subjects with age 45-55, 3 subjects with age 55-65, from both genders.
Both studies documented dramatic effects on various signs of skin aging from end users.
Define dramatic. I consider plastic surgery to be dramatic? Compare to that.
2. How is the active delivered? What vehicle? In what doses? Continuous vs discontinuous? How deeply does it penetrate?
The active is delivered by passive diffusion. The active is lipophilic, and is readily absorbed by skin.
Have you measured it? What you describe defies known stratum corneum absortion dynamics. The stratum corneum (SC) is a radically different biomembrane compared to other membranes in the body in function and composition. The SC is less permeable for lipophilic compared to the water-soluble compounds. Diffusion alone is rarely enough. Most botanically-derived substances e,g, antioxidants, vitamins) have great difficulty getting past the stratum corneum. Retinoids are an exception. But the stratum corneum would seem to be a weak place to carry out hormesis, due to its rapid turnover (memory effects) and the transformation of cells from metabolically active to organelle stripped as they mature from basement membrane to surface. Some measure of penetration seems to me to be crucial to support the hypothesis.
3. How is Glissandrin transported into cells to affect mitochondrial functions? By which known mechanism?
See above comments re: penetration.
Glissandrin is readily transported via diffusion into the cytoplasm and then mitochondria . The active compound is metabolized by cytochrome P-450 enzymes (in both cytosolic and mitochondrial compartments), with resultant generation of signaling ROS which in turn activate the MAPK/Nrf2 pathway. The consequent increased expression of antioxidant genes can enhance the mitochondrial antioxidant capacity and thus the mitochondrial ATP generation.
That is a concept that may works in cell cultures, but not in vivo. Nearly everything that happens in skin depends on active trans[port or some sort of receptor-triggered event cascade. Since the outer layers of the stratum corneum is metabolically speaking remarkably hypoactive, you need to explain how this would all work NOT in a culture of keratinocytes or fibroblasts, but in intact live human skin.
4. What cell populations in skin is it affecting?
As the active compound of Glissandra is bioavailable to all tissues in the body, it is reasonable to assume that Glissandrin is bioavailable to all types of skin cells.
You speak of “all tissues of the body” as though Glissandra is being ingested and transported via the circulation. That paradigm doesn’t hold for topically applied substances. First you have to show its site of deepest penetration/action (epidermis, dermis, subdermis), and if epidermal only, what layer (stratum corneum vs deeper epidermis). Very few substances get past the stratum corneum in physiologically active quantities. That is the function of skin – to keep things out. We have to assume that topical Glissandra is not arriving via the circulation.
You need to demonstrate what cells it is acting on and how it gets there.
5. If there is ROS signaling – what is the signal cascade? What other well known biochemicals are affected?
The signaling cascade involves the redox-sensitive MAPK/Nrf2 pathway. The activation of Nrf2 increases the expression of antioxidant genes such as enzymes in the glutathione antioxidant systems and superoxide dismutase, etc.
Yeah, but so does sunlight. How is this different that chronic UV exposure? A daily sunburn?
6. As with other mitochondrial stressors is there a shift toward anaerobic glycolysis?
Glissandra differs from other metabolic stressors in that it won’t increase the cellular energy demand and thus a shift toward anaerobic glycolysis.
Let’s focus on the ROS production and disposal, and its consequences. If Glissandra increases ROS production, what is the ROS disposal mechanism, and why is it good to keep applying an ROS stimulus (as a hormetic signal) after the hormesis has taken place? Why continue to use daily an ROS generating topical? Why would that not risk micro-inflammation, which would then become chronic, with other (undesirable) adaptations? Why not a sensitizing dose and then a booster say every 2-3 weeks?
Thanks for indulging our curiosity.
What happened to the debate? I keep coming back every day but nothing is happening.
Hi John. Sorry for the delayed response, I have been very busy with a couple of research projects.
Please find my responses below.
John: That would qualify as antioxidant. Yet (based on what you have said) first it raises ROS (reactive oxygen species). Would you then say it is an a pro-oxidant first (ROS contributor) but then upon adaptation to repeated ROS stress (the signal) it becomes antioxidant (ROS quencher) with time?
Robert: Yes. Glissandra serves as a pro-oxidant which generates signaling ROS that can activate Nrf2-mediated expression of antioxidant genes. The dependency on cellular enzyme (CYP) to metabolically generate ROS is self-limiting such that pathological events will not occur.
John: Visual trials with or without controls? Single arm studies without histology are extremely weak on the evidence scale. There are literally tens of thousands of such studies in the world of aesthetics, all generally saying the same thing. Are we to believe them all? It would help immensely to have some validation with split face, controls, serial histology, tape stripping for gene expressions or cytokines, etc.
Robert: The development of Glissandra as skincare product is based on the over 20 years of research on its Schisandra berry-derived active component, which has been shown to be able to enhance the mitochondrial structural and functional integrity in various tissues, particularly under conditions of oxidative stress. Topical application of the active component at certain critical concentrations was found to produce similar biological effects on animal skin tissue and cultured human fibroblasts. With the strong belief that the enhancement of Skin Qi – cellular energy status can increase the vitality of skin cells, we suggest the development of Glissandra as skincare product. The pre-market testing conducted on human subjects, though having low scientific merit as implicated, is instrumental to collect users feedback prior to the product launch. Surprisingly, Glissandra produces many unexpected beneficial outcomes in human subjects. As far as the basic research is concerned, the “Proof-of-Principle” testing outcomes support the postulated application of the active component in skincare product.
John: Define dramatic. I consider plastic surgery to be dramatic? Compare to that.
Robert: Many obvious improvements on skin before and after use which may not be as dramatic as those of “successful” plastic surgery. However, we believe that Glissandra offers a natural way to enhance the vitality of skin cells rather than doing spot fixing as in the case of plastic surgery.
John: Have you measured it? What you describe defies known stratum corneum absorption dynamics. The stratum corneum (SC) is a radically different biomembrane compared to other membranes in the body in function and composition. The SC is less permeable for lipophilic compared to the water-soluble compounds. Diffusion alone is rarely enough. Most botanically-derived substances e,g, antioxidants, vitamins) have great difficulty getting past the stratum corneum. Retinoids are an exception. But the stratum corneum would seem to be a weak place to carry out hormesis, due to its rapid turnover (memory effects) and the transformation of cells from metabolically active to organelle stripped as they mature from basement membrane to surface. Some measure of penetration seems to me to be crucial to support the hypothesis.
Robert: Given the low molecular weight and high lipophilicity of the active component of Glissandra, its bioavailability to skin tissue/cells should not be an issue. Whether or not hormetic response can be triggered in Stratum Corneum would also be dependent on the concentration of the hormetic agent. As long as mitochondria are present in the cells, Glissandra can produce the effect. After all, “dramatic” effect were observed in human users.
John: That is a concept that may works in cell cultures, but not in vivo. Nearly everything that happens in skin depends on active trans[port or some sort of receptor-triggered event cascade. Since the outer layers of the stratum corneum is metabolically speaking remarkably hypoactive, you need to explain how this would all work NOT in a culture of keratinocytes or fibroblasts, but in intact live human skin.
Robert: Sorry. I don’t see why the active component of Glissandra cannot elicit cellular responses in skin cells, either cultured or intact (in vivo), via the CYP-catalyzed ROS-mediated MAPK/Nrf2 signaling pathway.
John: You speak of “all tissues of the body” as though Glissandra is being ingested and transported via the circulation. That paradigm doesn’t hold for topically applied substances. First you have to show its site of deepest penetration/action (epidermis, dermis, subdermis), and if epidermal only, what layer (stratum corneum vs deeper epidermis). Very few substances get past the stratum corneum in physiologically active quantities. That is the function of skin – to keep things out. We have to assume that topical Glissandra is not arriving via the circulation. You need to demonstrate what cells it is acting on and how it gets there.
Robert: Topical application of Glissandra produces beneficial effect on skin tissues but not other tissues in the body. Oral administration of the active component of Glissandra was found to enhance the mitochondrial structural and functional integrity in various tissues.
John: Yeah, but so does sunlight. How is this different that chronic UV exposure? A daily sunburn?
Robert: Chronic UV exposure at a desirable (safe) dose can produce a similar hormetic antioxidant response. Whether or not the extent of UV exposure can be effectively controlled within a safe limit is questionable, not to mention a sunburn which is a manifestation of overdose. As mention earlier, the prooxidant effect of the active component of Glissandra is self-limiting (ie. safe).
John: Let’s focus on the ROS production and disposal, and its consequences. If Glissandra increases ROS production, what is the ROS disposal mechanism, and why is it good to keep applying an ROS stimulus (as a hormetic signal) after the hormesis has taken place? Why continue to use daily an ROS generating topical? Why would that not risk micro-inflammation, which would then become chronic, with other (undesirable) adaptations? Why not a sensitizing dose and then a booster say every 2-3 weeks?
Robert: A good question indeed. The signaling ROS is reduced by GSH (Glutathione), with resultant change in cellular GSH redox status, which in turn trigger the redox-sensitive signaling pathway and elicit antioxidant response. GSH will be regenerated from its oxidized form through glutathione redox cycling. Recurrent application of Glissandra is essential to keep this cycle working and set the cellular antioxidant machinery on a “ready” mode.
I look forward to continuing to share our science with you and your readers.
Since the last post from Professor Ko is August 2014, I’m looking forward to the 2docs’ responses. In my layperson’s view, however, I get the feeling that Professor Ko’s replies would be better served if he could provide links to any scientific peer-reviewed studies and/or articles that back up the product’s claims.
Also, could Professor Ko please clarify his answer to the question: Visual trials with or without controls? A simple: “The visual trials were without controls” or “The visual trials were conducted with controls” will suffice. If with controls, please explain what the controls were.
I supposed I could Google it, but what does “Proof of Principle” mean to scientific studies and in particular to this product?
Hi Dar, We will send this to the guys at Glissandra to awaken Dr Ko for an answer. Totally our fault that this debate slowed down – we have been extermely busy with so many things. But we will get back to it, soon we hope.
Hi Guys
Is this debate still active in February 2015 or are we at the end of the Science.
Best regards Tim
It’s not over, just resting. Can debates hibernate? . Not the fault of the Glissandra guys – it’s us at BFT who have been so very busy.