38 replies to this topic

[Mind]

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[Tom Andre F. (ex shinobi)]

Hi everyone.

 

I present to you here one of our products we are very excited about: A particular grape seed extract called Vitaflavan® that we sell here : https://www.dynveo.c...ed-extract.html

 

Our extract was used in a study done on mice, and was shown to boost in an impressive way their level of NAD+ :

 

source: http://www.nature.co...icles/srep24977

Dietary proanthocyanidins boost hepatic NAD⁺ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats

 

abstract:

Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD⁺) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD⁺ precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD⁺. Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD⁺ availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD⁺ levels.

 

What is awesome in this study is that the NAD+ boosting effect was even more impressive than what we seen using nicotinamide riboside, and the result seems more long term and different:

 

We see for instance Nampt was also increased by around 50%. It will help to convert dietary NAM (and the ones coming from NAD+ release) back into NAD+.

 

The method by which our grape seed did increase NAD+ is unclear but it did increase major NAD+ precursors such as Nicotinic acid or NMN. We can indeed speculate that taking this effectively helps to close the NAD loop and would help to elevate overall NAD levels.

 

The de novo pathway was particularly increased which is clearly a good thing:

 

"our results indicate that PAC (our grape seed extract) consumption increased the NAD⁺ levels by enhancing the de novo NAD⁺ biosynthesis pathway. Indeed, PAC increased the flux through the de novo biosynthesis pathway by overexpressing some of the key enzymes involved in this pathway and by increasing the precursor’s levels. In fact, the hepatic levels of Trp were robustly increased in a dose-response pattern, and it has been described that liver can increase the flux through the de novo pathway 40-fold when the levels of Trp or other NAD⁺ precursors increase. Together, these results strongly suggest that PAC consumption fosters the use of Trp in the liver as the main precursor of NAD⁺, while maintaining the activity of the salvage biosynthetic pathway at basal levels"

 

As a result, our grape seed extract "significantly reduced the hepatic lipid accumulation in a dose-dependent manner (Fig. 6A), and this was associated with a significant decrease in both the hepatic cholesterol and triglyceride concentrations (Fig. 6B)"

 

 

This resulted in a decreased expression for CD38 which is negatively associated with NAD+ level

 

 

Can these results being reproduced using a different grape seed extract than Dynveo® grape seed extract Vitaflavan® ?

 

Possible but unlikely.

 

The extraction process used to make this white grape seed Vitaflavan (the one used in this study) is unique. It is for instance the only extract we tested to contain more than 5% grape seed procyaninin B2, unlike less than 1% for all the other extracts we tested...

 

It is also the only one used as a standard in the US pharmacopeia and as mentioned in the study to possess such composition:

 

"the extract is mainly composed of phenolic compounds (total content higher that 96%) with the phenolic content composed of monomers or flavan-3-ols (21.3%), dimers (17.4%), trimers (16.3%), tetramers (13.3%) and oligomers (5–13 units; 31.7%) of procyanidins. The phenolic composition of this extract was further analyzed by Quiñones, M. et al.⁴⁵. Briefly, the analysis showed that the most important phenolic compounds contained in the extract were: catechin (58 μmol/g), epicatechin (52 μmol/g), epigallocatechin (5.50 μmol/g), epicatechin gallate (89 μmol/g), epigallocatechin gallate (1.40 μmol/g), dimeric procyanidins (250 μmol/g), trimeric procyanidins (1568 μmol/g), tetrameric procyanidins (8.8 μmol/g), pentameric procyanidins (0.73 μmol/g), and hexameric procyanidins (0.38 μmol/g)."

 

Most other brands also cheat and voluntary confuse consumer between polyphenols content and OPC content. The tests used are also often cheap and not reliable while we do use Gel Permeation Chromatography (GPC) as a gold standard.

 

If you have any questions please let me know

 

 

 

 

 

 

 

Edited by Mind, 05 December 2016 - 05:41 PM.

[ta5]

Is there evidence that procyaninin B2 increases NAD?

[Tom Andre F. (ex shinobi)]

Is there evidence that procyaninin B2 increases NAD?

 

I dont think so why ? What we do know is that this exact extract (so its full molecular spectro including high procyanidin B2 content) did increase NAD+. Others grape seed extract never share similar composition, they all are different since in your extraction process protocol change only one parameter for instance temperature or % solvants (and of course the solvants itselfs used) change the full result: you will attract and select only a fraction of a certain polarity etc. Most grape seed I studied do not care that level of details and speculate about OPC content based on polyphenols content cheap test method... Thats all I can say.

 

For procyanidin B2, the only study I found regarding NAD+ is this one:

 

Procyanidin B2 attenuates neurological deficits and blood-brain barrier disruption in a rat model of cerebral ischemia.

Abstract SCOPE:

Disruption of the blood-brain barrier (BBB) is a major pathogenic mechanism of neurological dysfunction and death after ischemic stroke. The aim of our study was to investigate the effect of procyanidin B2 (PB), a bioactive food compound, on BBB disruption induced by ischemic stroke and explore the underlying mechanism.

METHODS AND RESULTS:

PB was administrated intragastrically once a day starting at 3 h after transient middle cerebral artery occlusion (MCAO). PB treatment significantly decreased the infarction volume, brain edema, and neurological deficits after MCAO. PB prevented BBB disruption against ischemic stroke, as indicated by the reduction of Evans blue leakage and IgG levels. These results were also corroborated by immunofluorescence staining and Western blot analysis of ZO-1. Additionally, levels of reactive oxygen species and malondialdehyde were lessened in the ipsilateral ischemic area of brain by PB. The activities of antioxidant enzymes were elevated. Meanwhile, PB reversed the suppression of NF-E2-related factor nuclear translocation, and increased the protein expression of HO-1, GSTα, and NQO1 in the ipsilateral ischemic area of brain.

CONCLUSION:

PB attenuates neurological deficits and BBB disruption in a rat model of cerebral ischemia, and the neuroprotection of PB is associated with activation of NF-E2-related factor pathway.

 

 

So if you followed my posts in this forum, you know NQO1 is a key regulator / master gene to control high level of NAD+.

 

But once, again, for now what is sure and not a speculation is that our Dynveo® grape seed extract Vitaflavan® did increased in a dose dependent manner NAD+ in mice mainly via the de novo pathway.

[trakker]

Very interesting Tom.

 

 Minor question.  Your post says:

 

"The extraction process used to make this white grape seed Vitaflvaan"

 

the website you linked to says:

 

"an extract from the red grapes"

 

 

 

 

 

[Tom Andre F. (ex shinobi)]

You right ! Its a mistake. Our extract is from white grape seed and there is reason for this too. White grape seeds are low in tannins (high molar mass and then poorly absorbed) while white grape seeds owns more OPC with 2 to 5 rings

 

Here is an independent test made on our extract (Vitaflavan) : http://www.agilent.c...5991-0487EN.pdf

Edited by Tom Andre F. (ex shinobi), 05 December 2016 - 10:18 PM.

[Oakman]

Tom, I've been thinking/researching about your product's results and I have a question I can't seem to resolve. Please excuse my lack of understanding of these things.

 

Your research study says it provides elevated hepatic NAD+ and upregulating SIRT1, which obviously means in the liver. So I'm trying to understand the difference between producing NAD+ in the liver, and its effects....and the effect of producing NAD+ generally in the body cells by ingesting NR (or at least that's how I understand what NR does).

 

Is your extract's benefit limited to only to local use in the liver, or does the liver spread its  NAD+ far and wide in the body? Which goes back to my question in the NR experience thread about what significance overall is this extract?  So is 1 NR cap +1 Grape Seed Extract cap = what? in regards to overall NAD+ production in the body. Meaning, if I take NR and your supplement together, do I get ...2x NAD+production? 1.25?, or 3 or 4 times?   Again, with no human studies, this is conjecture of course, but maybe you have some ideas/theories. 

 

I'm trying to figure the cost/benefit ratio of taking your extract and or NR. If they are similar, or one is better than the other?  

 

You get my confusion, hopefully.

[Thell]

Oakman,

 

Refer to the end of the third paragraph in the discussion section,

Thus, the modulation of NAD+ homeostasis by PAC consumption empowers these compounds to modify a large number of metabolic processes in the liver. Furthermore, the liver exports NAD+ precursors to other organs, such as the brain and muscle, which have a lower capacity to synthesize NAD26. Thus, as several organs depend on NAD+ homeostasis in the liver, the modulation of NAD+ homeostasis by PACs could be extended as a general effect in the whole organism.

 

where the reference is to Dissecting Systemic Control of Metabolism and Aging in the NAD World: The Importance of SIRT1 and NAMPT-mediated NAD Biosynthesis which may answer the 'local' part of your question.

 

It may be worthwhile to note...

 

The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

 

...We next evaluated the efficacy of NR, NMN and NA to increase NAD+ in vivo by supplementing mouse chow with NR, NMN or NA at 400 mg/kg/day for one week. All compounds increased NAD+ levels in liver, but only NR and NA significantly enhanced muscle NAD+ content. (Fig.1D). These results illustrate how NR administration is a valid tool to boost NAD+ levels in mammalian cells and tissues without activating GPR109A.

→ source (external link)

 

and

 

Novel NAD+ metabolomic technologies and their applications to Nicotinamide Riboside interventions

 

We dissected the livers and muscles18 from mice after either gavage19 or intraperitoneal injection (IP) of 185 mg/kg body weight NR Cl or mole equivalent of Nam and NA and analyzed using LC-MS/MS. Saline injections were also performed. The liver NAD metabolome exquisitely responded to all three precursors; however, NR displayed unique and superior effects in increasing NAD+ (four-fold compared to two-fold after Nam and NA) after gavage (Figure 5.2b).

→ source (external link)

 

 

[tunt01]

Congrats on your excellent results Tom.  Have you tested or do you have plans to test SIRT3 or MnSOD2 at all?

 

Thanks.

[Thell]

Hi Tom,

I'm guessing that since this is now on the market (thanks for that and congrats) that you, and perhaps some others, have been consuming it. Do you, by chance, have any anecdotal experiences to share? I'm particularly wondering if there may be enough of an increase in Trp with a 50mg dose that possible effects on mood/memory could be experienced.

[Tom Andre F. (ex shinobi)]

@Thell, thank you for this review. Indeed the liver is a good and strategic target to test NAD+ since it serve as a pool then for others organ. I just mention that here the way how we increase NAD+ is still important.

 

NR was used in your study in molar equivalent than Nam and NA means they used twice of it, than the 2 others, to make all things clear. Plus, NR act mainly via Nam as confirm this study with the Nam peack following NR consumption, and as did another study you can maybe give me back the link here where they knocked down the mice in Nampt. So you have finally

 

All organs do not owns the kinases to express NAD+ with NR, especially the NRK2 wich seems to be the more relevant. For instance immune cells or adipocyte, but still NR will increase NAD+ since they owns Nam salvage pathway. (https://www.ncbi.nlm...pubmed/18429699). Its still a problem as we age we have an Nampt leakage wich become extracellular and promote cytokine..

 

The fact ou grape seed increase NAD mainly via anti inflammatory effect (CD38) and de novo pathway is important.

 

@Prophets, thanks we actually did not test it ourself, its independent scientist that did using our extract as its the only 'valid' grape seed extract on the market with proper data and used in the pharmacopea US. I can still submit your idea to test on SIRT3, but its something hard to test as far as i know, since you need to induce a certain stress prior to it to see result / difference, so we need expert in this field.

 

 

 

 

 

Edited by Tom Andre F. (ex shinobi), 08 December 2016 - 09:36 PM.

[Tom Andre F. (ex shinobi)]

Hi Tom,

I'm guessing that since this is now on the market (thanks for that and congrats) that you, and perhaps some others, have been consuming it. Do you, by chance, have any anecdotal experiences to share? I'm particularly wondering if there may be enough of an increase in Trp with a 50mg dose that possible effects on mood/memory could be experienced.

 

Hi Tell,

 

Well I use it since more than a year here in france though my french brand of the same name, and take one 100mg pill per day in the morning. Its hard to say on me as I take some others supplements such as pterostilbene.. But still looks really young (most people think im under the 25yo while im 30, what is funny is that i looked 24 since 19yo).

 

I also feed my grand father with it since a few month to increase his bad cognitive function and poor blood circulation, and it seems to be of some success because for instance he is more easy to found his keys or to drive and he has less 'blue' marks on the skin.

 

But all these are anecdotal evidence. What we need is to increase our NAD+ as much as we can still

[yucca06]

It's funny...I've read about your product there, and I live in France (not very far from your Lab address). I'm going to order a few bottles of your OPC product to see if I feel something more than NR.

Oh, and you've got pterostilben too 

[Tom Andre F. (ex shinobi)]

ahah yes we have also the french company of the same name We are currently moving our lab very near by Montpellier.

 

 

[Ark]

Any discount code for longecity?

[Tom Andre F. (ex shinobi)]

Any discount code for longecity?

 

Sure, here is a promo code for longecity: LONGCITY34 (will give you a 10% discount on your total order)

 

 

Cheers

Edited by Tom Andre F. (ex shinobi), 15 December 2016 - 03:58 PM.

[pamojja]

ahah yes we have also the french company of the same name

 

As a European would prefer to order from the french site. However, the 2 stores don't seem to carry the exactly same products. Does that change anytime in the future? The discount code will work on both sites?
 

[Tom Andre F. (ex shinobi)]

Yes you right, they are not only 2 differents website but also actually 2 differents company: dynveo.com is dynveo LLC while dynveo.fr is dynveo SARL

 

So I dont know yet for the product range, I communicate here as dynveo LLC.

 

For the code I will request from them to allow this code and let you know here once its done. Thanks for your interest

 

[Tom Andre F. (ex shinobi)]

discount code LONGCITY34 also work for dynveo.fr

 

[pamojja]

Thanks for letting us know, and answering all concerns. 

[normalizing]

i dont understand why not all grape seed extracts do this. obviously this trademark one is the only one tested for increase in NAD, but if this one does it, why would there be speculation others do not

[Tom Andre F. (ex shinobi)]

i dont understand why not all grape seed extracts do this. obviously this trademark one is the only one tested for increase in NAD, but if this one does it, why would there be speculation others do not

 

I think I was clear enough in my first post...

 

The real question is not "why would there be speculation others do not" but rather "why would there be speculation others can do"  ?

 

because there you totally change the protocol !

 

I understand for many grape seed extract = grape seed extract but this is so so wrong from a chemistry point of view

 

First, many brands volontary confuse OPC and polyphenols wich is definitely not the same, OPC are a subclass of polyphenols and request deeper and more expensive testing

 

Second, this extract is the most concentrated on the market, purely...

 

Third, when you extract you have to use extraction (so a certain recipe) + purification proces (another recipe) + drying process (another recipe) :

 

• So each extract use differents grape seeds (for the record, all grape seeds owns different chemical profile.. this is fact, the one we use comes from white grape from Bordeaux, 33, Most famous place for wine quality in france)
• And each recipe (what solvents, what ratio, what duration etc) make the final product also totally different from the others.

 

Again, I could speak about this topic for hours but you cant compare an extract to another in terms of effect if you dont look that deep. For instance we have at least 5 times more procyanidin (yes I repeat...) there than ALL others suppliers we tested, this has both a direct impact (grape seed procyanidin B2 owns lot of effect, see studies..) and indirect: impact on the final molecular ratio, see my first post once again

 

At the end, if you understand all this, feel free to order from a different source, but just be aware such speculation are not acceptable from a scientific  point of view as you change the full protocol, or found an extract that owns similar chemistry profile and if you do, please send me it by PM as we virtually tested all suppliers on the market, even some from china

 

Cheers

[normalizing]

well, i was taking nicotinamide riboside for a while for energy and it didnt help, not sure what to expect from grape seed extract in terms of "boosting NAD". what should one expect when "boosting NAD" to begin with? if nicotinamide riboside didnt help me with energy and other mental and physical issues, i suppose its just not for me

[LOOKINGFORTIME]

How does the group feel about Life Extension's Grapeseed?

serving Size 1 vegetarian capsule

Amount Per Serving

Vitamin C (as calcium ascorbate)

250 mg

Calcium (as calcium ascorbate)

25 mg

Proprietary Blend:

100 mg

Masquelier’s®2 Original OPCs1 [single and condensed (2-5) units of flavanols & polyphenols from grape seeds]

Leucoselect®3 grape seed extract [std. for 95% proanthocyanidins]

Trans-Resveratrol [from Japanese knotweed (root) and whole red grape extracts] [also supplying glycosides (polydatin)]

20 mg

Trans-Pterostilbene (from pTeroPure®)

0.125 mg

Other ingredients: vegetable cellulose (capsule), microcrystalline cellulose, silica, vegetable stearate.

1- Oligomeric proanthocyanidins are powerful antioxidants that help protect cells and tissues from free radical-initiated damage.
2- MASQUELIER’s® is a registered trademark of International Nutrition Company BV (INC), Loosdrecht, The Netherlands.
3- Leucoselect® is a registered trademark of Indena S.p.A.
pTeroPure® is a registered trademark of ChromaDex, Inc.

Dosage and Use

• Take one (1) capsule daily with or without food, or as recommended by a healthcare practitioner.

Warnings

• KEEP OUT OF REACH OF CHILDREN
• DO NOT EXCEED RECOMMENDED DOSE
• Do not purchase if outer seal is broken or damaged.
• When using nutritional supplements, please consult with your physician if you are undergoing treatment for a medical condition or if you are pregnant or lactating.

To report a serious adverse event or obtain product information, contact 1-866-280-2852.

[normalizing]

hmm looks like they use high class patents for their formula thats what i notice and i expect it to be expensive too

[LOOKINGFORTIME]

till about the 31first  if you are a member it is   22.95 for 4 bottles   1 bottle is 24.30

 

I wonder, though, are the mg's  high enough per cap?

[Tom Andre F. (ex shinobi)]

First this brand use fillers I wouldnt touch, especially calcium

 

Second, these suppliers used here, are exact exemple of what I tried to explain, they make no difference between polyphenols and OPC instead what is wrote there. the confusion is volontary. Again, OPC are a subclass of polyphenols.

 

We tested them too for the procyanidin B2 test for exemple...

 

Third, thanks to not discuss this into another thread as this one is sponsored, thanks for your understanding.

 

Cheers

[LOOKINGFORTIME]

Great got it, thank you for telling me that.

[Journey2016]

How many people are using the grapeseed in the link? Looking for feedback, ive recived my order today.

[Oakman]

I had been using it in the PM (using 200mg, 2 pills) instead of another 250mg NR (taking 500mg NR AM). Nothing bad, nothing noticeable either... from NR or GSE.