Uncut- A New Encapsulated Pre-Workout From Applied Nutriceuticals

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    Uncut- A New Encapsulated Pre-Workout From Applied Nutriceuticals


    You heard it here first- a little teaser info about the product- release in a few weeks

    Uncut FAQs and Write-Up (partial, we will fill in the blanks as the launch date nears)

    Game-Changer, Genius, Revolutionary, Next-Level
    : These are adjectives thrown around constantly by supplement companies, for every product release. Everything is the next best thing, till it isn’t- you hear these claims so often, they get diluted a little more with each new pre-workout released on the market. Talk is cheap- results are everything- is your “concentrated” pre-workout a diluted mess of clumpy flavors, fillers, and ingredients that you have never heard of? Applied Nutriceuticals wants to change this- we are taking the “fluff” completely out of pre-workout supplementation with a concept so innovative and potent that it will be copied for years to come. Want to add 3-5 more reps to each set, and 25-50 lbs. to each major lift- do I have your attention now? Get to the source, and get rid of the flavored crap- get UNCUT™ from Applied Nutriceuticals. UNCUT™ is 90 capsules of raw motivation in a bottle- a pre-workout pill that provides intense stimulation and focus, while providing animal physical neuromuscular strength- accomplished through a completely unique formulation. With Uncut™, Applied Nutriceuticals is the first company to actually pay attention to ingredient half-lives when formulating a pre-workout- and it will truly take your workout to a whole new level of intensity- F^&K 1 more rep, get 5!! UNCUT™ delivers concentrated contraction within every working muscle fiber (and we mean EVERY fiber) to deliver can-crushing, phone-book ripping strength and intense skin-splitting pumps! Your days of shoveling mounds of clumpy, foul-tastiing pre-workout powder into a shaker cup and chugging it down are over- get to the source: pure, potent, no-nonsense: UNCUT™.
    The Basics:
    -“THE” Only Truly Concentrated Pre-Workout- in a Capsule
    -90 Capsules of Raw Strength in a Bottle; No Powders, Flavors, or Fluff
    -Destroy Plateaus and Never Have an “Average” Workout Again
    -Laser Focus with Intense Lasting Energy and Skin-Splitting Pumps
    -Warning: Due to rapid strength gains of 25-50 lbs. on each major lift, muscular strength may outpace tendon strength- use accordingly

    Frequently Asked Questions


    1. How long before a workout should Uncut™ be taken? 20-30 minutes
    2. How long do the energy-enhancing effects of Uncut™ last? 3-5 hours
    3. How is Uncut™ different from my normal pre-workout? Uncut™ is encapsulated- no need for shaker cups or mixing clumpy powder; just take Uncut™ with 12 oz. of water to be ready to hit the weight room.
    4. What is a normal dose for Uncut™, and is there a dosage that should never be exceeded? The normal dosage for Uncut™ is 1-3 capsules; 1 capsule for smaller individuals, and people who are not very tolerant to stimulants, 2-3 capsules for stim-tolerant individuals and people who weigh over 200 lbs. ***Do not exceed 4 capsules in a 4 hour period***
    5. Uncut™ doesn’t contain arginine, or nitrates, but still provides a strong pump, why does it do this? Uncut™ provides a pump through the selective stimulation of β2 adrenoceptors, which have been shown in research to increase nitric oxide levels and vasodilation in skeletal muscle; Uncut™ also heightens sensitivity to nitric oxide, and allows for levels of cyclic AMP and cyclic GMP in smooth muscle to remain elevated through phosphodiasterase inhibition; all of these characteristics are helpful in increasing blood flow to skeletal muscle and allowing for greater pumps during your workout.
    6. Does Uncut™ contain 1,3 DMAA? And will it be as strong as products that contain 1,3 DMAA? Uncut™ does not contain 1,3 DMAA; and yes, it is as strong or stronger in terms of energy compared to products that contain 1,3 DMAA.
    7. Is Uncut™ NCAA-compliant? No, it contains a banned stimulant; all stimulants including caffeine are banned by the NCAA.
    8. I have a medical condition, should I check with my doctor before I take Uncut™? Yes, always consult your doctor before beginning any supplement regimen.
    9. How quickly will I see results from Uncut™? Uncut’s™ effects on energy enhancement occur within 20-30 minutes; generally strength and rep increases from the product occur within the first couple workouts after beginning Uncut™.
    10. Can I stack my normal pre-workout product with Uncut™? No, we do not recommend this- due to the unique properties of Uncut™ this will not be necessary.
    11. Will Uncut™ help me burn body fat as well? Yes, several of the ingredients are useful for lipolysis.
    12. Do I take Uncut™ with food, or on an empty stomach? Taking Uncut™ on an empty stomach is optimal, but it can be taken with food; however, food will lessen the effects, at least somewhat.
    13. Can I take Uncut™ other times during the day, just for an energy boost? This is not recommended because of the strength of Uncut™, plus, the effects of Uncut™ tend to diminish with time if overused; Black Cats® is a better option for an additional energy boost during the day.
    14. What can I stack with Uncut™ with? Uncut™ can be used with Drive during a workout for extreme pumps, as there are ingredients in Drive that will potentiate the effects of Uncut™. Uncut™ can be stacked successfully with any Applied Nutriceuticals product, as long as it is used in a pre-workout capacity.
    15. Are there any other products that I should not take with Uncut™? Avoid other strong stimulants while taking Uncut™- and this entails other pre-workout powders that contain stimulants.
    16. How much water should I drink per day while taking Uncut™? Try to drink at least 100 oz. of water per day while taking Uncut™; research has documented that a hydrated muscle is a much stronger muscle.
    17. Will Uncut™ suppress my appetite? Yes, using Uncut™ will temporarily decrease your appetite.
    18. Where can I buy Uncut™? Any retailer or e-tailer listed at Applied Nutriceuticals | Pre Workout Supplement, Fat Burner, Nutritional Supplements, Weight Loss Supplement


    Here are a couple of the ingredients- more coming later- stayed tuned for the final formula- it is pretty awesome:

    -Amentoflavone (from Herba selaginella)-
    Bioavailability- marginal; logP 5.09; use of p-glycoprotein inhibitor may improve this (piperine or naringin)
    Onset- Undetermined, from data gathered may be accumulated readily in system over multiple uses
    Tᵐᵃᵡ- Undetermined; calcium-releasing effects in SR may take several administrations to manifest

    A biflavone found in Gingko biloba, Hypercium perforatum, Herba selaginella, and many other herbals; amentoflavone has some very unique properties. The compound antagonizes GABA-A receptors, inhibits acetylcholine esterase (AChE), increases calcium release from the sarcoplasmic reticulum in skeletal muscle, can act as an inhibitor of phosphodiasterase (non-specific; seems to be geared mostly towards 4 and 5), and can modulate the insulin pathway. SAR (Structure Activity Relationship) data has shown that amentoflavone can potentially bind to multiple pharmacological targets; in Uncut™, the mechanisms of greatest interest are the ability to inhibit AChE (see above), to reduce phosphodiasterase (PDE4 and PDE5), and the propensity to increase calcium release from the SR in skeletal muscle (see below vs. Caffeine structure) (6,9,10). Suzuki, et al. 1999 found the following: “Amentoflavone, like caffeine, caused a concentration-dependent increase in Ca2+ release from the heavy fraction of fragmented sarcoplasmic reticulum of rabbit skeletal muscle. The Ca2+-releasing activity of amentoflavone was approximately 20 times more potent than that of caffeine….. amentoflavone was not changed by caffeine, but was further increased by adenosine-5′-(β,γ-methylene) triphosphate. This compound enhanced [ ]ryanodine binding to the heavy fraction of fragmented sarcoplasmic reticulum with a decrease in KD but without a change in Bmax. These results suggest that amentoflavone, which does not contain a nitrogen atom, probably binds to the caffeine-binding site in Ca2+ channels and thus potentiates Ca2+-induced Ca2+ release from the heavy fraction of fragmented sarcoplasmic reticulum.” (9,10)
    Another study by Dell’Agli M et al. (2006) found that “Ginkgo biloba dimeric flavonoids (GBDF) were shown to inhibit cAMP phosphodiesterase activity and to promote vasorelaxation. In particular, amentoflavone exhibited endothelium-dependent relaxation of rat aorta rings via enhanced generation and/or increased biological activity of nitric oxide, leading to elevated cGMP levels. The aim of this study was to investigate whether GBDF were able to inhibit cGMP-specific phosphodiesterase-5 (PDE5) as well. Human recombinant PDE5A1 was prepared by expression of the full-length cDNA of PDE5A1 in COS-7 cells. The PDE activity was determined in the presence of biflavones at 0.1-100 microM. All biflavones inhibited PDE5A1 in a concentration-dependent fashion, ginkgetin being the most potent (IC50 = 0.59 microM). The ability to inhibit the enzyme followed this order: ginkgetin > bilobetin > sciadopitysin > amentoflavone > sequoiaflavone. These data suggest that GBDF could exert a vasodilating effect through a mechanism independent of NO release.” (5) PDE5 is an enzyme that binds and hydrolyzes cyclic guanidine monophosphate (cGMP), a second messenger responsible for vasodilatory functions in skeletal muscle (among other functions); by inhibiting PDE5, amentoflavone can allow for higher amounts of cGMP to accumulate in skeletal muscle tissue, allowing for greater venous activity. Note the structural similarities between sildenafil, icariin, and amentoflavone (below; all of which have PDE5-inhibitory activity), and cGMP; According to Chen (2009) SAR activity dictates: (1) Hydrophobic compounds tend to be more potent PDE-5 inhibitors; (2) Because of the big binding site, inhibitors with molecular weights over 500 remain potent; (3) From the pharmacophore analysis, the features of hydrogen bond acceptors are the basis for designing novel inhibitors of PDE-5 and (4) According to MLR analysis, the number of ring groups could be up to 6, but the number of aromatic rings was limited to 4 to be potent.” (12) This signifies some PDE5 inhibitory activity for amentoflavone, but due to the higher number of ring groups (6) and a higher molecular weight (538 g/mol), this effect may not be as “enhanced” as some of the other “pharmaceutically”-tweaked PDE5 inhibitors (sildenafil and the like)with a lower molecular weight and a lesser numerical ring structure. Another related aforementioned characteristic of amentoflavone is PDE4 inhibition; PDE4 specifically hydrolyzes adenosine 3',5'-cyclic monophosphate (cAMP) to inactive adenosine monophosphate (AMP)(11,12,39,40,48). This effect is fairly obvious in the structural comparisons between cAMP, Roflumilast (a pharmaceutical PDE4 Inhibitor), amentoflavone, and Moracin M; interestingly, none of the herbal PDE inhibitors contain an aliphatic amine (or nitrogen for that matter) and have multiple polar hydrogen atoms, which indicate that they will have little or no BBB permeability. Amentoflavone retains these characteristics, and does retain some specificity for the PDE4 binding pocket, thus allowing greater amounts of cAMP to accumulate in multiple types of peripheral tissue. Using Moracin M (which has been assayed for specific PDE4 binding sites) as an analogue due to their similar structural characteristics (especially to apigenin, of which amentoflavone is a homologue dimer), one can extrapolate some similarities to amentoflavone in binding characteristics to PDE4 (6,14-15,20,23-24,28). Chen et al. (2012) found that Moracin M “inhibited PDE4D2, PDE4B2, PDE5A1, and PDE9A2 with the IC(50) values of 2.9, 4.5, >40, and >100 μM, respectively. Our molecular docking and 8ns molecular dynamics (MD) simulations demonstrated that moracin M forms three hydrogen bonds with Gln369, Asn321, and Asp318 in the active site and stacks against Phe372.”(15)

    -Caffeine Anhydrous-
    Bioavailability- high; logP -0.55
    Onset- Rapid, generally 5-10 minutes
    Tᵐᵃᵡ- variable; 30-60 minutes
    Trimethylxanthine stimulant compound that produces effects in the CNS and also on the metabolism; there is also evidence that caffeine may inhibit AChE (see above in reference to Huperzine A/ACh SAR). Caffeine is both water- and lipid-soluble, and can penetrate the BBB, and readily antagonizes adenosine receptors (especially A₁ and A₂ᴬ). By antagonizing A₁ (which mediates the flow of calcium into the neuron) and A₂ᴬ (which regulate adenylate cyclase activity), caffeine can influence the dopaminergic system and also the sleep/wake cycle. Adenosine binding also appears to suppress tyrosine hydroxylase, which is needed to convert tyrosine into L-Dopa, which is a major step in catecholamine production. Caffeine has been shown to have the ability to release calcium from the sarcoplasmic reticulum (SR), an effect that can improve the contractile force of skeletal muscle (16,29): “Caffeine also potentiates CICR (Calcium Induced Calcium Release), but unlike ATP, it increases the Ca2+ sensitivity of CICR in addition to the maximum response at the optimal Ca2+ concentration……In mammalian skeletal and cardiac muscle, however, a high concentration of caffeine induces Ca2+ release via RyR in the virtual absence of Ca2+ (0.08–2 nM), provided that Mg2+ is absent…… Although the rate of CICR is much lower than the rate of physiological Ca2+ release, the usually undetectable CICR becomes detectable when it is potentiated by caffeine….. Caffeine at high concentrations can induce contracture of skeletal muscle without changing membrane potentials. At lower concentrations, it can potentiate twitches without changing action potentials and can shift the relation between membrane potentials and activation to a more negative potential in potassium contracture and in voltage-clamp experiments without changing the charge movement of t-tubule voltage sensor.” (16,29)

    Caffeine has been shown to enhance muscular contraction in relation to athletic performance in multiple studies; A study by Bazucchi et al. in 2011 on adolescent males (human study) found that caffeine increased muscle fiber conduction velocity and maximal dynamic muscular contractions in the biceps brachii. The researchers found that contractile force was enhanced significantly after caffeine supplementation, which supports the hypothesis that caffeine has a positive effect on motor unit recruitment (17). Astorino et al. (2010) found that caffeine dose-dependency was a factor in caffeine-related force production; researchers discovered that doses of 2 mg/kg of caffeine before exercise did little to improve isokinetic muscular function, while a dose of 5 mg/kg produced a significant enhancing effect on force production (2).
    Dirk Tanis, BA, MSci
    Chief Operating Officer, Applied Nutriceuticals

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    Yikes!
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    Oh man, this is going to be huge....
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    Whats the ETA look like for this?
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    Quote Originally Posted by Piston Honda View Post
    Yikes!
    You heard it here first Just wanted to throw a little bit out to our peeps
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    Quote Originally Posted by JudoJosh View Post
    Whats the ETA look like for this?
    3-4 weeks
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    NO Uptake + Uncut = Best Workout Ever?
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    There are a total of 9 active ingredients, plus vitamin/mineral co-factors....
    Dirk Tanis, BA, MSci
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    Quote Originally Posted by jimbuick View Post
    NO Uptake + Uncut = Best Workout Ever?
    We are working on something similar to, but more potent than NO Uptake......and yes, the new products will stack together phenomenally well
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    Quote Originally Posted by rms80 View Post
    There are a total of 9 active ingredients, plus vitamin/mineral co-factors....
    Any hints on the ingredients? Like pathways that are utilized?

    Sent from my SAMSUNG-SGH-I727 using Tapatalk 2
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    Quote Originally Posted by rms80 View Post
    We are working on something similar to, but more potent than NO Uptake......and yes, the new products will stack together phenomenally well
    I'm a big fan of Uptake so that sounds awesome!
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    I love the warning disclaimer given!

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    How come none of these made it into my package with NO Uptake???

    In for more info.
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    Quote Originally Posted by bolt10 View Post
    How come none of these made it into my package with NO Uptake???

    In for more info.
    Because they gave them all to me. :P
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    this sounds glorious.
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    Subd
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    Awesome news. RPM still hanging around though? Love the stuff.
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    Quote Originally Posted by Cordeen View Post
    Awesome news. RPM still hanging around though? Love the stuff.
    Hope so

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    Quote Originally Posted by Cordeen View Post
    Awesome news. RPM still hanging around though? Love the stuff.
    This will actually be a big upgrade of RPM- stronger stimulant component, better pump, better strength gains, better formula through more recent R&D; RPM has been on the market for almost 6 years now (so has Drive)- kind of hard to believe......

    We will be sending out samples of Uncut very soon- stay tuned in so you can find out how to try the product- we will also be running some really aggressive contests and promos over the next few weeks as well
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    Quote Originally Posted by JudoJosh View Post
    Any hints on the ingredients? Like pathways that are utilized?

    Sent from my SAMSUNG-SGH-I727 using Tapatalk 2
    You have a couple pathways in the ingredient descriptions above- but here are a couple:
    1. Excitation-contraction
    2. CICR in skeletal muscle for longer, harder muscular contractions (noticeable strength and rep gains)
    3. Inhibition of PDE4 and 5 (pump)
    4. Synchronization of ingredient half-lives (important)

    Several more, but I will post these over the next couple weeks.....
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    Quote Originally Posted by Cordeen View Post
    Awesome news. RPM still hanging around though? Love the stuff.
    I love RPM myself, but UnCut IMO is way better.
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    Quote Originally Posted by jdg76 View Post
    I love RPM myself, but UnCut IMO is way better.
    I second this. Uncut + Drive is so much win.
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    Waiting on the next Betas!! Come on Rms80!! LOL
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    Quote Originally Posted by rms80 View Post
    This will actually be a big upgrade of RPM- stronger stimulant component, better pump, better strength gains, better formula through more recent R&D; RPM has been on the market for almost 6 years now (so has Drive)- kind of hard to believe......

    We will be sending out samples of Uncut very soon- stay tuned in so you can find out how to try the product- we will also be running some really aggressive contests and promos over the next few weeks as well
    now you have my attention....kind of a rpm drive combo in one with added stims.....hell yeah!!!

    4 caps of rpm uncaaped in chrystal lite used to be my fav...
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    Quote Originally Posted by thebigt View Post
    now you have my attention....kind of a rpm drive combo in one with added stims.....hell yeah!!!

    4 caps of rpm uncaaped in chrystal lite used to be my fav...
    Is that actually tolerable? Because RPM is horrid uncapped. I imagine Uncut to beat that out without having to open the capsules.

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    Quote Originally Posted by OrganicShadow View Post
    Is that actually tolerable? Because RPM is horrid uncapped. I imagine Uncut to beat that out without having to open the capsules.

    -OS-Team AppNut
    lol...it isn't pleasant....i am always interested in new stim formulas since the fda's seems intent on banning all the old school formulas that worked so well.
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    Quote Originally Posted by thebigt

    lol...it isn't pleasant....i am always interested in new stim formulas since the fda's seems intent on banning all the old school formulas that worked so well.
    So they can keep America fat along with their wallets bc their hands r in The pockets of insurance and doctors???... Woa whered that come from
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    Quote Originally Posted by chedapalooza View Post
    So they can keep America fat along with their wallets bc their hands r in The pockets of insurance and doctors???... Woa whered that come from
    lol....don't you go and get me started....
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    Quote Originally Posted by thebigt View Post
    lol....don't you go and get me started....
    The formulation is DSHEA-compliant, so I don't think we are going to have any issues.......
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    Quote Originally Posted by rms80 View Post
    The formulation is DSHEA-compliant, so I don't think we are going to have any issues.......
    i wish you much good fortune....i am glad to see innovation is still at play. i know that when rpm was 1st released it was cutting edge, hopefully you will have the same success with uncut!!!
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    I'll believe it when I see the dose of amentoflavone
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    The above is my own opinion and does not reflect the opinion of PES
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    What's going on in here?
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    Quote Originally Posted by Nugget5 View Post
    What's going on in here?
    Who are you? Strong post to rep power ratio...
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    Quote Originally Posted by Dewey99 View Post
    Who are you? Strong post to rep power ratio...



    My sig won't show up, guess I need a certain amount of posts? I need to get used to this forum and check around

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    Quote Originally Posted by mr.cooper69 View Post
    I'll believe it when I see the dose of amentoflavone
    W/O giving away the formula, 200-300 mg of the 20% per 3 capsules (so 40-60 mg pure material)- not a cheap compound, but when you hit threshold, you really notice it, especially for focus and strength- dosage is really dependant on what you use it for- it is a PTP-1 inhibitor as well (think insulin pathway)- bioavailability kind of sucks ass (high logP), but with a p-glycoprotein inhibitor present, it may slow efflux (at least somewhat)- very hydrophobic (5.09), so even w/o efflux there may be some substance that kicks back through the lipid bilayer
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    Quote Originally Posted by mr.cooper69
    I'll believe it when I see the dose of amentoflavone
    I was excited see this as this is one of the two new DSHEA compliant stimulants in HTP blog that I haven't tried.

    Good stuff AppNut!

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    So when amentoflavone and caffeine in the product stimulating a release in calcium, would it be wise to supplement calcium alongside uncut for long term use?
  

  
 

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