The Creation and Execution of an Ingredient Program - Polyphenolics MegaNatural BP - An Interview with Dr. Anil Shrikhande and Dr. T. C. Kappagoda

By Len Monheit

The following interview represents one of those satisfying moments in this industry. You see, several years ago, I had the opportunity to speak with Polyphenolics’ Dr. Anil Shrikande and UC Davis’ Dr. T. C. Kappagoda about an ingredient program they were working on, the former from a business standpoint and the latter from a clinical research program point of view. At that time, the program was in its relative infancy, but I am very pleased to say, the program has evolved both for business and research, pretty much according to plan. As we all know, that doesn’t happen that frequently in our industry. And through it all, Polyphenolics has maintained its commitment to the science, and consistent with that mission, is participating in this year’s Nutracon as the Antioxidant Science Track sponsor.

We’re now following up that 2006 interview and closing the loop on three years of program evolution.

Interview with Dr. Shrikhande - March 2010

Dr. Shrikhande, it’s now been over 3 years since you and I last talked about Polyphenolics and MegaNatural®. What have been the highlights of the past 3 years for the company?

We’ve seen strong growth overall due to innovation and marketing of MegaNatural BP®.

Over the past 18 months, some organizations have performed well, others less so. What has it been like for Polyphenolics and what do you see in the future?

It’s been very good. We’ve had a solid growth pattern for the past 18 months, with approximately 50% overall growth. Our major category focus remains dietary supplements with some functional beverage opportunities being explored for major brands.

Where have been your channel successes?

Our greatest success so far has been in retail and MLM. We’re now focusing on the mass market. We’ve certainly been on track with our strategy so far and expect that to continue.

How does Polyphenolics operate within such a large multinational such as Constellation Brands Inc.?

We are vertically integrated and the operation reports to Constellation Wines US. We are a really unique contributor and have high visibility within the organization. In this case it’s actually a huge company working within a huge company.

Who are the most typical consumers of products with your ingredients?

We do have some information on this. A typical user would seem to be about 35 years old and the ratio male to female is about 30 to 70. We don’t really know how accurate this is since this number can be distorted depending on how many females actually are buying for men. While we do try to track this information, since we’re not that directly connected with this data, we don’t have much leverage.

Now let’s turn to the real subject of this discussion. When we spoke several years ago, you were in the launch stages for MegaNatural®. Let’s start with what’s transpired since…

Frankly, MegaNatural- BP® has become the front runner in the field. Several things have happened. First of all, our manufacturing process in the winery is tight. It’s so consistent, beginning with the grapes and absolutely focused on quality. We produce different products with different processes – it’s under absolute control. Second, for MegaNatural BP®, this has been our first real successful attempt to develop and bring to market a health condition targeted product. Our clinical program with UC Davis is continuing under the direction of DR. Kappagoda, who continues to publish and has recently awarded a patent for method of use for our MegaNatural-BP.

Is the program on track from a business/market standpoint? What’s next?

At this point, it’s going very well, from both a customer and consumer point of view. We continue to see the same customers continuing to buy even more product, a very positive sign. Mostly, we’re focusing on our customers and providing them a health-targeted product. We are different from the other grape seed extract providers and so we’ll continue to build our platform, including clinicals, new technology etc.

From a marketplace point of view, where are your key successes?

Our relationship with GNC is certainly successful, as well as that with New Chapter. We’ve got product into Vitamin Shoppe, as well as with several MLM companies where typically grape seed extract dominates but now MegaNatural BP® is well positioned.

What areas have traditionally been less successful?

I think we really have to get to mass. The prices there will ultimately be a bit lower but it does not seem to have many products that effectively compete and of our caliber. We’ve really started focusing there this year.

Is there competition? How do you compete? How now does co-branding work for you?

‘BP’ really has none, as it has intellectual property protection on both the process and the science. It’s a very specific product and a composition you can actually track. We’re identifying BP to emphasize the quality of both retail and MLM products, mostly retail though.. Cobranding requires logo of MegaNatural-BP on the back panel. Consumers are noticing this logo as producer of superior quality grape seed extract. You can see this logo in most of the GNC products related to heart health.

What are the competitive advantages for Polyphenolics in this market over European and Asian suppliers?

Well, relative to grape seed extract there’s a lot to offer. Firstly, serious competition from China has subsided due to quality issues and a lack of science. With our vertical integration and constant control of quality, well that’s not necessarily the case even in the EU or elsewhere in the world. And of course, we’ve got the largest operations in the world with major wineries in US in California, Australia, Canada, New Zealand, and partnerships in Europe.

What kinds of things are your customers saying? What are consumers saying? How have you measured both of their interest?

Our customer response has been strong – we all believe it’s a growth category. They’ve asked for other products too. They’re happy to co-brand which is a great sign. We also indicate that they have to use the appropriate quantity and they’re happy to do so. Feedback from consumers is a bit more difficult but we do have some on the website including lots of questions about MegaNatural BP®. Traffic to the website www. is consistently growing.

How important is your IP position? Has the investment in research been worthwhile?

It is absolutely critical to our plans to effectively manage our IP. And as to research, we think it is very worthwhile. It has paid itself off very quickly as the product has come to market. Without clinical science it is very difficult to sell. Dietary supplements need to and are moving to this environment where clinical research and science is absolutely fundamental.

What lessons have you learned along the way from this product experience?

You need products with clinical research to show results. That’s what consumers buy products for.
Has there been any reaction to the work your company is doing from the medical community?
On this topic, we really haven’t investigated, but may in the future.

Do you have any other observations or messages?

You need consistency and quality. With Polyphenolics, one of the keys has been simple messaging. You need a product whose health effects are measurable. If not, what are we really doing guys?

And I want to mention that for me personally, my responsibility has changed from R & D to 100% on Polyphenolics business, marketing and sales. I’m totally focused on Polyphenolics, and that means much more engaged in its business and the industry itself.

Interview with Dr. T. C. Kappagoda, March 2010

Since our 2006 discussion, what has been the evolution of the research on MegaNatural BP®?

In 2006, we were starting our human program, we had done some preliminary work on blood vessels, showing that MegaNatural BP® made them relax, and this was the starting point for our human work. We initially pursued Mechanism of Action experiments and once confirmed, went into human studies on 1) blood pressure and 2) other promising things that we’re currently investigating.

Has your UC Davis research been published in peer reviewed scientific journals and conference proceedings?

Yes, it has been both published as well as been the subject of international presentations. In Metabolism we published our work on Metabolic Syndrome and the blood pressure work associated with pre-hypertension was presented at an international meeting and there was a publication stemming from that as well. We’ve also got several papers pending, including our work on changes in blood concentration ie bioavailability. In 2008 we published our work on the mechanism of action of grape seed extract in the journal Clinical Science.

What is the IP status of the UC Davis research on reduction of blood pressure?

Polyphenolics has an exclusive license agreement with University of California to distribute MegaNatural-BP in several countries where PCT patents have been filed as IP. The US patent was recently awarded to University of California.

How does endothelial relaxation influence blood pressure?

From in vitro studies, we know that relaxation is totally dependent on good endothelial function. If this function is impaired, there is no relaxation. In humans, we can also relax blood vessels, and when the action of grape seed extract is involved, it acts on receptors on the cell surface, phosphorylating a protein, AKT, on the cell wall. This involves a biochemical pathway called PI3K which in turn activates an enzyme called eNOS ( nitric oxide synthetase ), which in turn triggers the release of nitric oxide which then relaxes the vessels. We have experimental evidence that if this pathway is blocked, there is no relaxation. In this case, we worked with a human endothelial cell culture showing that when we methylate the hydroxyl functionality of procyanidins in grape seed extract, we block the relaxation.

Outside of blood pressure in metabolic syndrome, what other markers have been studied, as part of this project?

We have consistently found metabolic syndrome interesting as it has the potential to affect a large population. As you know, this condition is referred to when an individual has three of five characteristics, namely, abdominal obesity, elevated blood pressure, elevated blood glucose, high triglyceride levels and low HDL. With metabolic syndrome, one in two eventually will become diabetic with associated elevated risk of coronary artery disease. If we approach this logically, we start to deal with this issue which costs huge amounts of dollars to the health care system, as well as having significant human impact. We’re now focusing on the question of whether, as the incidence of diabetes rises, does grape MegaNatural-BP also have a place in that conversation? As a strong antioxidant, it may have a role. In one of our approaches, we’re examining the typical Western meal which contains up to forty percent fat. This consumption triggers an increase in post-prandial fat production, as well as triggers an inflammatory response (chemicals are released etc). This takes time to resolve and settle down so for the second meal of the day, at noon, there is a second stress, without full recovery, and this continues without complete resolution through the day. The result of this stress is to prevent insulin from working properly. This is evident in metabolic syndrome. So we’re trying to see whether grape seed extract can reduce the inflammatory response through its antioxidant activity. We have IRB approval to begin exploration of this very interesting area of research of critical importance.

There is also a place in the case of heart failure. Patients with heart failure have a very poor outlook. The current course is mostly palliative treatments and the five year mortality is quite high. Some treatments help but we’re trying to see whether antioxidant activity can effect this situation in a positive way. We expect much of this work to be done by the end of the year.

You’ve done some work with methylation of the extract too. What did that show and what does it mean?

These were the controls in the in vitro study. The hydroxyl groups attach to the phenol group in a REDOX reaction, so here, we eliminated the hydroxyl groups, expecting an inert molecule and that’s exactly what happened. We controlled the experiment, eliminated the effect therefore showing that the antioxidant was the source of the activity.

Could you talk a bit about the dose response?

We evaluated dose response in two contexts. First, in vitro, when we began our work on grape seed extract, we really had no idea about target concentration etc. so we went by the level that would be associated with a level in blood based on wine consumption. In our human work we needed to fix a dose, which we did by evaluating certain polyphenols consumption information and then Constellation Wines applied for their GRAS affirmation relative to the upper levels of these polyphenols. We arrived at 300mg of the grape seed phenolic compounds per day, but in the literature the number does vary widely. We then approached this from the safety profile and determined that 300mg seemed quite acceptable and in our research we used both 150 and 300mg on a daily basis, and from MegaNatural BP® in metabolic syndrome, observed no difference at these levels. Since this is new territory though, we’re using 300mg as our working dose as that level has proved safe.

Have there been any safety issues in recent trials?

No, there have been none. We’ve now had experiments involving up to 50-60 people and have had no problems and seen no safety issues. Polyphenolics has done other studies at several institutions and found nothing troubling at comparable doses. There is also lots of data on companies using ORAC and other methods of measuring antioxidant activity and levels and the ORAC value per gram of grape seed extract is higher than natural functional foods with once again nothing to indicate safety issues.

Has the in vitro work been predictive of in vivo research? Any surprises?

I guess if anything, we are surprised that our cell culture work panned out so much; we’ve seen nothing suggesting anything different from our expectations. As I mentioned, if we see some results in our examinations regarding heart failure, it would be great news.

What about bioavailability?

In these studies we found grape seed procyanidin monomers in blood plasma in human clinical subjects by special HPLC tests conducted by Ron Pryor, a well known figure in procyanidin and ORAC research from USDA.

What’s next in this research program?

As noted, we’re excited by our course of work on heart failure, as well as the continuation of our metabolic syndrome post-prandial studies where we’ll be investigating a meal with grape seed extract as part of it versus placebo. If it works as anticipated, we’ll then move to looking at a whole day and at that point, it we’re on track, we’ll be very excited.

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