Questions from Dr. John and the answers from Prof. Robert in the BFT debate

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  drjohn

  JULY 29, 2014 AT 5:01 PM · REPLY

  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.

Professor Robert Ko

August 2, 2014

Dr. John, please find below my answers to your questions.

Respectfully, Robert

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!

Seriously though, Glissandra has been shown to protect against oxidative damage induced by solar light irradiation both in vivo and in vitro.

Two clinical trials using Visual anti-aging assessments were conducted. The duration of the studies were 8 weeks. Data collected were tabulated and analyzed.

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.

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.

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.

3. How is Glissandrin transported into cells to affect mitochondrial functions? By which known mechanism?

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.

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.

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.

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.

The debate focuses on mitochondrial decay and mitohormesis

More from Craig on Glissandra

JULY 26, 2014 AT 7:09 PM · REPLY

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

i Mortality 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).
ii Vitamins in Aging, Health, and Longevity, David R Thomas; The Division of Geriatric Medicine, Saint Louis University Health Sciences Center, Saint Louis, MO, USA.

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  drjohn

  JULY 26, 2014 AT 10:40 PM · REPLY

  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.

Professor Robert Ko

JULY 29, 2014

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

Show me the Science! Show me the Results! Don't show me Photoshop!

I thought I would share some photos of real customers that have used our anti-aging skincare line with Glissandrin™.

There is always controversy when people look at before and after photos. This is because of the explosion of photos on the internet and company websites and ad campaigns that are obviously photoshopped or altered in some way.

They just are not believable. Let's take a look at a post on the BFT website.

http://barefacedtruth.com/2014/05/25/ladies-tell-us-doesnt-get-just-little-pissed-ceramides-part-1/

I mean really, do you believe this isn't photoshopped?

How about this one - I mean seriously! No wonder nobody believes before and after photos!

So how do you show a before and after photo and have people believe they are real?

First, I believe that a selfie is much more believable than a professional photo. A photo you take of yourself with your smartphone is much more likely to be real.

Second, make sure the public, yes YOU, can see who the person really is. YOU can see they are not an actor or stock photo. I am sure we all have seen examples of the same before and after photo being used in different ad campaigns for different companies! How do you accomplish this? Simple. Put a link to the person's Social Media page so you can see they are a real person. Someone you can connect with and even pick up the phone and speak to.

Third, I believe the best before and after photo is your own photo. If you don't see personal results, how can you convince others how effective the product is.

Having said that, here are my own photos. I just took a photo today, which marks just over 9 months of using Glissandra on a daily basis. I'm a guy...I'm a bit lazy and I only use it on average once a day in the mornings. You can find my LinkedIn profile at: ca.linkedin.com/pub/craig-peloquin/86/540/649

Let me share a couple of recent after photos taken on July 11th. I was there with Susan and Ron when the photos were taken and I helped them upload their before and after photos to their LinkedIn profile. 

This is Susan Brillon and her LinkedIn profile can be found at: ca.linkedin.com/in/susanbrillon

Here is Ron Borse and his LinkedIn profile can be found at ca.linkedin.com/pub/ron-borse/8a/693/9a7

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Retinoids and Retin-A

This post is in response to a BFT reader, Robert who posted:

Robert

JUNE 27, 2014 AT 5:04 AM · REPLY

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.

http://barefacedtruth.com/2014/06/25/from-theory-to-glissandra/#comment-130907

Robert,

Wow! It certainly doesn't take much to derail a debate on the science. The purpose of this debate is to discuss the science behind the ingredients. Glissandra contains Glissandrin™, a proprietary blend of Schisandrin A, B, C and (-)B, not "goop".

If you want to discuss the benefits of Tretinoin, that's great. We can post some of the science and side effects behind retinoids. There are no known side effects to Schisandrin B.

Audrey Kunin, MD on http://www.dermadoctor.com/blog/retin-a-retinoids-retinol-vitamin-a-creams/ writes:

Retin A was developed more than 30 years ago as an acne treatment. It's actually a twisted form of the Vitamin A molecule. Dermatologists prescribe it not just for acne but for a wide variety of other skin concerns that respond to exfoliating agents and "keratolytics" (a product that removes a plug out of a hair follicle or sweat gland. Since then a wide range of prescription molecules have been developed as well as their cosmetic counterparts.

Here is a link to read more about the side effects:

http://www.medicinenet.com/tretinoin-topical/page2.htm#SideEffects

I still don't see what this has to do with our marketing term, Bioceutical.

Craig

Hormesis and Schisandrin B

So Dr. John and Dr. George have done a cursory investigation of Schisandrin B and have some questions regarding hormesis.

"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."

Okay, so let's address hormesis. Hopefully these links will make it easier for Dr. John, Dr. George and the BFT readers to see more than just a cursory look at our science.

Professor Ko has offered up 3 papers he has published on this topic.

The first:

Frontiers in Research:
Herbal Bioactive Molecules: The Hidden Jewels for Drug Development
Mitochondrial decay in ageing: ‘Qi-invigorating’ schisandrin B as a hormetic agent for mitigating age-related diseases

SUMMARY

1. The mitochondrial free radical theory of ageing (MFRTA) proposes a primary role for mitochondrial reactive oxygen species (ROS) in the ageing process. The reductive hot spot hypothesis of mammalian ageing serves as a supplement to the MFRTA by explaining how the relatively few cells that have lost oxidative phosphorylation capacity due to mitochondrial DNA mutations can be toxic to the rest of the body and result in the development of age-related diseases.
2. Schisandrin B (SchB), which can induce both a glutathione anti-oxidant and a heat shock response via redox-sensitive signalling pathways, is a hormetic agent potentially useful for increasing the resistance of tissues to oxidative damage. The enhanced cellular ⁄mitochondrial anti-oxidant status and heat shock
response afforded by SchB can preserve the structural and functional integrity of mitochondria, suggesting a potential role for SchB in ameliorating age-related diseases.
3. Future studies will focus on investigating whether SchB can produce the hormetic response in humans.

Click here for a link to the study

The second

Schisandrin B as a Hormetic Agent for Preventing Age-Related Neurodegenerative Diseases

SUMMARY

Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of neurodegenerative diseases, with the latter preceding the appearance of clinical symptoms. The energy failure resulting from mitochondrial dysfunction further impedes brain function, which demands large amounts of energy. Schisandrin B (Sch B), an active ingredient isolated from Fructus Schisandrae, has been shown to afford generalized tissue protection against oxidative damage in various organs, including the brain, of experimental animals. Recent experimental findings have further demonstrated that Sch B can protect neuronal cells against oxidative challenge, presumably by functioning as a hormetic agent to sustain cellular redox homeostasis and mitoenergetic capacity in neuronal cells. The combined actions of Sch B offer a promising prospect for preventing or possibly delaying the onset of neurodegenerative diseases, as well as enhancing brain health.

Click here for a link to the study

The third

Schisandrin B enhances the glutathione redox cycling and protects against oxidant injury in different types of cultured cells

SUMMARY

Tert-butylhydroperoxide (tBHP) challenge caused an initial depletion of cellular reduced glutathione (GSH), which was followed by a gradual restoration of cellular GSH in AML12, H9c2, and differentiated PC12 cells. The time-dependent changes in cellular GSH induced by tBHP were monitored as a measure of GSH recovery capacity (GRC), of which glutathione reductase (GR)-mediated glutathione redox cycling and c-glutamate cysteine ligase (GCL)-mediated GSH synthesis were found to play an essential role. While glutathione redox cycling sustained the GSH level during the initial tBHP-induced depletion, GSH synthesis restores the GSH level thereafter. The effects of (- )schisandrin B [(- )Sch B] and its analogs (Sch A and Sch C) on GRC were also examined in the cells. (- )Sch B and Sch C, but not Sch A, ameliorated the extent of tBHP-induced GSH depletion, indicative of enhanced glutathione redox cycling. However, the degree of restoration of GSH post-tBHP challenge was not affected or even decreased. Pretreatment with
(- )Sch B and Sch C, but not Sch A, protected against oxidant injury in the cells. The (- )Sch B afforded cytoprotection was abolished by N,N0-bis(chloroethyl)-N-nitrosourea pretreatment suggesting the enhancement of glutathione redox cycling is crucially involved in the cytoprotection afforded by (- )Sch B against oxidative stress-induced cell injury.

Click here for a link to the study

And here is just a quick response to this post.

http://barefacedtruth.com/2014/06/25/from-theory-to-glissandra/#comment-130371

drjohn

JUNE 26, 2014 AT 3:25 AM · REPLY

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.

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.

Scientific debate with BareFacedTruth.com

I have been going back and forth for the past few weeks with Dr. John and Dr. George who run the blog, www.barefacedtruth.com.

They were intrigued with the science behind our products and asked if we would start a debate with them.

I have been following the BareFacedTruth blog for a number of months now, and it seems that no other MLM company was willing to back up their scientific claims, but then, no other MLM company has as much science behind their product like Glissandra does.

http://barefacedtruth.com/2014/06/25/from-theory-to-glissandra

To make this debate fair, we have both agreed to post our comments on each other's blogs. This way neither blog has the upper hand in the debate.

We are debating the science, not the MLM business model.

We encourage everyone to participate in asking questions about the science, and let's leave the MLM debate to another time and place.

So the rules are simple. Please don't plug Glissandra or the business opportunity. Sharing your personal stories about the product is fine, but make sure you don't exaggerate your testimonials. Truth Matters!

I know all of our Glissandra members are passionate about our products, and this debate is designed to showcase our science not our business plan.

You can ask questions about any ingredient in any product, as we have our doctors and their doctors monitoring the debate. I can't think of a better way to discuss the Theories of Aging and the science behind it.

Craig

Schisandra Berry

Here are some great links to get more information on the Schisandra Berry.

Chris Kilham, the Medicine Hunter, created a great video on location in North Eastern China at a Schisandra Berry Farm.

Here is a link to the video: http://youtu.be/O6nk05irmPA

Here is a link to his website: http://www.medicinehunter.com/schisandra

He also showcased the Schisandra Berry on the Dr. Oz show. Here are the links:

http://www.medicinehunter.com/schisandra-dr-oz1

http://www.medicinehunter.com/schisandra-dr-oz2

Speaking of Dr. Oz show, here is the link to segment on the Glutathione, our bodies Master Antioxidant. Schisandrin B helps to increase and recycle the Glutathione levels in your cells.

Here is the link to the show segment: http://youtu.be/4dh34aa_0Ng

Here is a link to the research paper: http://www.ncbi.nlm.nih.gov/pubmed/17119269