quigs
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Phenogen was probably the best product that I've ever used for fatloss and recomp. Since its discontinuation, I've been patiently awaiting a suitable replacement. It finally seems that everything that I'd need to make my own version is available except for GPA. I can't find this stuff anywhere, unless its mixed with creatine (which is not what I want).
I know there was some talk about NP possibly bringing back phenogen at some point, but I was really hoping that in leu of this that you could provide bulk GPA for those who wish to make their own.
Right now, I'd really like to try a DCP/Phenogen hybrid by stacking DCP with low dose sesamin and GPA.
Here's some more info on GPA for those interested from Avant's phenogen writeup:
Introducing PhenoGen: Spook Knows Fat Loss
I know there was some talk about NP possibly bringing back phenogen at some point, but I was really hoping that in leu of this that you could provide bulk GPA for those who wish to make their own.
Right now, I'd really like to try a DCP/Phenogen hybrid by stacking DCP with low dose sesamin and GPA.
Here's some more info on GPA for those interested from Avant's phenogen writeup:
Introducing PhenoGen: Spook Knows Fat Loss
GPA is a creatine analog. Unless you have been living under a rock for the last year you know there is quite a bit of controversy and disagreement about this compound. Obviously since I have included it in Phenogen I tend to think it can be highly beneficial for body composition if used in a cyclic fashion. You can basically think of GPA as an exercise amplifier.
Normally when a muscle contraction first begins there is a spike in the demand for ATP. ATP is the currency of energy you cell traffics in. It is used to fuel cellular reactions by donating a high energy phosphate and in the process it becomes ADP. ATP gives up its phosphate quite readily. ADP on the other hand is quite a bit more stable and it is less likely to give up its phosphates. Still, if there is enough demand some reaction will steal yet another phosphate from ADP and in the process form AMP. This is exactly what happens when you begin a high intensity muscle contraction. There is a sharp rise in demand that can not be met by either oxidative phosphorylation or glycolysis. So for first few seconds of a contraction there is a demand for phosphates that can not be met. During this time AMP concentration skyrockets as reactions steal phosphates from ATP and ADP. A few seconds later the cell has kicked in its energy production system whether that’s glycolysis (fast twitch) or oxidative phosphorylation (slow twitch).
This increase in AMP activates the enzyme AMPK. I have written quite a lot of about AMPK in my articles on leptin so take a look if you’re interested. The main things that AMPK does that we are interested in are as follows:
Increase fat oxidation by inhibiting ACC.
Increase GLUT4 translocation and concentration of GLUT4.
Increase mitochondrial enzyme concentration.
Increase the number of mitochondria per cell.
Increase creatine transporter density.
Increase beta-adrenoceptor density (125% in one study).
Increase the production of glycogen synthetic enzymes.
Further decrease in DGAT1 activity in adipose tissue.
GPA works because it enters cells just like creatine but it is not a suitable substrate for creatine kinase (CK). CK is the enzyme responsible for attaching a phosphate to creatine. Creatine then acts as a battery of sorts. It’s a store house for excess phosphate that can be donated when energy is in high demand. Thus GPA gets rid of this battery effect and makes your cell rely on nutrients like carbs, fat, and protein to produce ATP. That additional oxidation adds up. For example in one study rats fed beta-GPA for 8 weeks showed a 45% increase in mitochondrial ATP synthesis. Also, because of this it creates a greater AMP signal to activate AMPK because creatine phosphate is not present to donate its phosphate to ADP, turning it back in to ATP. So you get much stronger AMPK activation.
It’s basically a cardio amplifier. It will cause your cells to undergo many of the adaptations that they undergo when exercised.
It induces fat burning by deactivating an enzyme called ACC that inhibits the use of fat for fuel. By doing so it will promote the use of fat instead of carbohydrates for fuel post exercise to accomplish things like protein synthesis and lactic acid conversion. This should synergize well with the other two ingredients. Sesamin will increase the amount of CPT in your cells which is the rate limiting compound in fat oxidation. SM will increase FFA availability by decreasing TAG output. Both SM (though enhanced leptin sensitivity) and GPA will activate AMPK disabling ACC which inhibits CPT. So you get all three working in tandem to maximize fatty acid oxidation.
One of GPA’s benefits is in promoting mitochondrial proliferation (26). One of the greatest benefits of exercise is increased mitochondrial density. The rate limiting step in fat oxidation is an enzyme called CPT. CPT is resident on the mitochondria’s membrane. So more mitochondria means more membrane surface area which means more CPT. This increase in mitochondrial density is also quite advantageous as it reduces the oxidative stress on any given mitochondria. In other words it distributes the damaging free radicals that are a necessary byproduct of substrate oxidation across more mitochondria so there is less damage per mitochondria. This is though to be one of the reasons exercise is so healthy. After all exercise is known to produce lots of oxidants. But because of mitochondrial proliferation the load that must borne by a single mitochondria is reduced.
GPA will enhance the translocation of the GLUT4 glucose transporter to the cells surface (27). This makes it an excellent glucose disposal agent and it should aid in reducing plasma insulin levels that are often elevated in those who are overweight.
Before I told you a little bit of a fib when I stated that lipolysis is irrelevant. Well not so much a fib. More like I was using over zealous language. I did this on purpose because I wanted to try to shock you, the reader, in to honestly examining the need for increased lipolysis from fat cells. I said that I thought stimulant based fat burner like ECA or clen work through interaction with muscle tissue. One of the ways I think they do this is via increased lipolysis in muscle tissue. Muscle also stores fats called intra myocellular lipids (IML). This is possible because skeletal muscle also contains DGAT1. Skeletal muscle also contains HSL that is up regulated by beta-adrenoceptor binding just like in fat cells. When HSL is activated it frees these lipids for use as fuel. It seems that beta-adrenergics like clen or ECA also help preserves muscle mass while dieting. It just so happens that GPA increases beta-adrenoceptor density in skeletal muscle (28). In other words GPA should give you better results when stacked with stimulant based lipolytic supplements.
Finally let me pose a question to you. If DGAT1 in adipose tissue is so important how do you think your body controls it? We learned earlier that ASP is what turns it on but what turns it off? It just so happens that it is AMPK activation in fat tissue that naturally turns it off. (29) Not only that but AMPK also inhibits GPAT so it also prevents fat storage at the beginning of the storage pathway.
Since there is so much controversy about GPA I feel it’s warranted to take some time to examine some of the issues surrounding this compound. Much of the criticism seems to revolve around the idea that it will promote the conversion of fast twitch to slow twitch muscle fibers. Most body builder and athletes loath this idea as it’s the type II fast twitch fibers that provide explosive strength. This could indeed be bad if it actually occurred. However, I think peoples concerns are misplaced this time around. My only guess is that people have not done a through investigation of this compound.
You see there is some rat research that shows that phosphate depletion through GPA does indeed case fast to slow twitch conversion. There are even a few that examine the expression of myosin isoform subtypes (30). The problem is the studies are not applicable. You see the bulk of these studies did not take in to account the age of the rats before the treatment with GPA was started. One study tried to bring to light this discrepancy (31). In this study they tested GPA administration to four week old rats and eight week old rats. Four week old rats are considered juveniles. This is right about the time they are weaned. Eight week old rats are considered adults. Their body has basically stopped growing and its physiology has been fixed. They then fed both these young rats and adult rats GPA. After 40 days on this diet they examined the rats. What they found was that in the young rats there was indeed a shift in muscle fiber type and a dramatic change in myosin heavy chain isoform towards the slow twitch variety. However in the adult group there was no such change at all. This makes a lot of sense when you think about it. There are certain times during an organism’s life cycle when it is particularly susceptible to environment imprinting and childhood is one such time. So these studies showing fast to slow twitch conversion are not really applicable to humans. To accomplish the same thing and individual would have to take GPA through there entire adolescence. It would be rather like growing up malnourished.
It also makes sense that it should not effect fast twitch fiber conversion if you think about how it works. I know there is not a lot of discussion about creatine anymore as everyone has pretty much just concluded it works. But there is a lot of very interesting research telling us how it works. For example you would think that creatine would work primarily by increasing phosphate stores in glycolytic fast twitch muscle fibers. This is not the case however. It seems that creatine content of fast twitch fibers is already maxed out for the most part. Most creatine uptake is actually in slow twitch oxidative fibers and sarcoplasm tissue (32). In fact it seems that much of creatines benefits revolve around increasing endurance and recovery of oxidative muscle tissue. Since GPA works though creatine transport mechanisms it’s not that surprising that GPA would mainly affect oxidative type I fibers and sarcoplasm tissue in adults. This is exactly what has been found in numerous studies.
There are quite a few studies that compare the soleus and extensor digitorum longus (EDL) muscles (33,34,35). The soleus is primarily oxidative slow twitch and the EDL is glycolytic fast twitch. Just about every single study finds the same things. In the slow twitch fibers there are sharp and dramatic increases in mitochondrial density and increases in mitochondrial oxidative enzymes like cytochrome c oxidase, but not much degradation of the ATP/ADP ratio. Considering the bulk of GPA is going in to this kind of tissue this means that the cell has dramatically increased nutrient use to make up for the loss of the creatine phosphate system. In the glycolytic fast twitch cells there is no increase in mitochondrial density and little increase in oxidative phosphorylation enzymes. Instead there is dramatic increase in demand for carbohydrates. The cell dramatically increases ATP synthesis activity, increase citrate synthesis activity (lowers fat oxidation), increases GLUT4 translocation, and shows a dramatically altered ATP/ADP ratio. So in fast twitch is not able to compensate as well as oxidative muscle fibers. In glycolytic fast twitch muscle it appears to just dramatically increase its use of carbohydrates for fuel.
Still there appears to be no muscle fiber conversion from fast to slow twitch. If you fear a loss in strength there is probably little worry there as well. Creatine depletion was studied in female rats using GPA (34). What they found was that there was no loss in maximal tetanic stress which is a measure of the intensity of muscle contraction. Even better when the GPA depleted rats were supplemented with creatine following the GPA use there was a sharp increase in muscle creatine content and a statistically significant increase in tetanic stress. Thus there appears to be a rebound effect when creatine is given after a cycle of GPA. This is exactly how I recommend Phenogen be used as you will see below.
There is one big downside to GPA however. It needs to be cycled thus Phenogen needs to be cycled as well. One of the older studies on GPA sheds light on this issue (36). When GPA was administered to rats it resulted in the changes described above. Namely, increased substrate use and all mitochondrial and enzymatic adaptations. However this was after twenty two days of GPA use. The study was then continued and after sixty six days the levels of these enzymes actually went down instead of up. This makes sense upon examination. Initially the body adapts and increases substrate use and does all those wonderful things however as time goes on the cell begins to think it is in a state of food shortage. Thus it lowers metabolism to try and minimize its fuel usage. Now these time frames can be extended out quite a bit for humans. Rats have much faster metabolisms than humans so they adapt much more quickly than us. Still it is not something that should be used indefinitely.
