Synergistic stacking…..who believes in doing it?

[T3/T4 GSR]

my current cycle is -
Test e - 500mg week
Deca - 300mg week
dbol - 50mg a day
Ran the dbol for 6 weeks and running deca for 10 and test for 12....possibly 14 if I am close to my goals but don't quite make it. PCT will be aromasin and nolva

[BajanBastard]

I was looking yesterday for it...Vitor, can you please post a list of the different AS that act on the mediated and non-ar mediated mechanism please.

The injectables are the A.R binders and the orals (cept Var) are the non-A.R binders.

Yeah Skull cycle looks nice for me the test with be used for TRT and aromatization for better muscle gains when using tren .

[stupidhippo]

canu baja clarify that statement... u mean they bind less to the AR?

[BajanBastard]

The 17AA steroids don’t bind to the A.R and promote anabolism via other mechanisms of action.


Strong binders to the A.R

Trenbolone
1-testosterone
Oxandrolone
Drostanolone
Nandrolone
Methenolone
Mesterolone
Metribolone
Boldenolone
Stanolone
Stenbolone


Low/non binders

Furazabol
Methandrostenolone
Chlordehydromethyltestosterone
Oxymetholone
Stanozolol
Methyl-1-testosterone
Superdrol
Fluoxymesterone

[stupidhippo]

yeah I also have heard that they are relatively low-binders but still what the textbooks say its still their primary mechanism of effect. What are the other mechanisms, are they known? Im interested in this if u happen to have a link or sumin with credibility. Dbol for one has been studied alot and to my understanding its primary way of action is still AR nevermind if it has other mechanisms of action.

[oswaldosalcedo]

OSWALDOSALCEDO how does the tren oral work? is it an acetate?...by the way i'm also using win/dbol in 75/125 respectively mon-fri(training days) with EQ.

yeah acetate,all are fast roids, 8 hours active life.
(my own reasons).

[oswaldosalcedo]

yeah I also have heard that they are relatively low-binders but still what the textbooks say its still their primary mechanism of effect. What are the other mechanisms, are they known? Im interested in this if u happen to have a link or sumin with credibility. Dbol for one has been studied alot and to my understanding its primary way of action is still AR nevermind if it has other mechanisms of action.

yes,stronger affinity it does not imply necessarily a more intense action at the receptors, there is no linear relation.

[guest589745]

The 17AA steroids don’t bind to the A.R and promote anabolism via other mechanisms of action.


Strong binders to the A.R

Trenbolone
1-testosterone
Oxandrolone
Drostanolone
Nandrolone
Methenolone
Mesterolone
Metribolone
Boldenolone
Stanolone
Stenbolone


Low/non binders

Furazabol
Methandrostenolone
Chlordehydromethyltestosterone
Oxymetholone
Stanozolol
Methyl-1-testosterone
Superdrol
Fluoxymesterone

Are the means by which these cause growth etc known exactly? I have read that Dbol is supposed to activate the pituitary and release GH according to a study done on rats.

???

[cantspeak]

One rather key issue to usage of anabolic /androgenic steroids (AAS) is how one chooses which to use, or which combination to use, and indeed, why combinations might be superior to comparable amounts of single steroids. The issue of combining AAS for most efficient muscle gain is one that has been entirely neglected in the medical literature, since acquisition of muscle is not considered of therapeutic necessity, and observations by bodybuilders have unfortunately generally not been made in a systematic manner. I cannot yet give definitive and complete answers on this matter, but some things are clear at this point, and general support for the principle of synergy can be found in some scientific studies.


--------------------------------------------------------------------------------

Pharmacology in the Simplest Case

First, let us consider the case of the simplest kind of drug. This drug would act in only one way, and would do so by binding to a receptor and activating it. The amount of activity performed by that type of receptor would be directly proportional to the number of receptors that bound the drug. Nothing else of any kind would be going on with this drug.

There might also be similar drugs which worked the exact same way, binding to the same receptor. The only ways in which these drugs could differ from the practical point of view are in pharmacokinetics (how fast each drug enters and clears the body) and how potent each drug is. The latter term is one that may easily be misunderstood due to common usage differing from scientific usage. Potency refers to how little of a drug is required to give a defined amount of effect. For example, if one may obtain the desired therapeutic effect in 50% of subjects with 1 mg/day of Drug A or 100 mg/day of Drug B, then Drug A is 100 times more potent.

This does not mean that Drug A is necessarily better! One can get the same effect from Drug B simply by using 100 times as much. It might be the case that Drug B might be preferable despite the higher required dose: for example, if Drug A leaves the body too quickly or too slowly, or has more toxicity for the same therapeutic effect. It means only that in comparing the drugs, to compare them equally, one must compare the effects of 1 unit of Drug A to 100 unit of Drug B.

To understand this a little more, unfortunately we have to use a little math. One could skip over the math if desired and just look at the conclusions which follow fairly easily from the numbers calculated.

Drugs and receptors interact with each other according to a simple equation:

(conc. of drug) (conc. receptor)
Kd = -------------------------------------
(conc. of drug « receptor)

where (conc. of drug « receptor) is the concentration or amount per volume of receptors that have drug bound to them, and (conc. of drug) and (conc. of receptor) refer to the concentrations of free drug and receptor respectively.

This number Kd is a constant (always the same) for any given drug, but will vary between drugs of different potencies. This fact allows us to calculate the percentage of receptors occupied if we know Kd and the amount of drug.

Kd will be expressed in units of concentration, for example, 1 nanogram per liter. More potent drugs have lower Kd values. In our comparison of Drugs A and B where A was 100 times more potent, if Drug A had a Kd value with the receptor of 1 ng/L, then drug B would have a Kd of 100 ng/L: you would need 100 times more of Drug B to get the same effect.

What would happen therapeutically if you "stacked" Drug A and Drug B?

You can play with the math and you will find that using blends of A and B, where one keeps in mind that B is 100 times less potent and therefore uses 100 mg of it for each unit of A it replaces, that one gets the exact same result regardless of the stacking. Let’s say that Drug A comes in 1 mg tablets and Drug B comes in 100 mg tablets. Each tablet therefore gives the same effect. In the case of the simplest type of drug such as these two drugs, the effect is identical whether one uses 10 tabs of A, 10 tabs of B, or 5 tabs of each. The same number of receptors are occupied regardless and the effect is the same.

Therefore, stacking these drugs makes about as much sense as stacking two brands of aspirin or two brands of coffee. It is okay if one happens to have both available, but there is no reason to go out and buy the second brand in the hopes that stacking it will give more of a caffeine buzz, or more pain relief.

The mixing might make sense if there were a pharmacokinetic difference: perhaps one of the brands of aspirin is time-released and you want both an instant hit for immediate pain relief as well as sustained action. (The sustained action though could be obtained with only the regular brand, simply by taking small amounts frequently.)



--------------------------------------------------------------------------------

Application to AAS

Now the obvious question here is, Is the same type of drug response true with AAS, or are more complex things going on? Let’s say that, used alone, the same effect is obtained from 1 "Deca -unit" of Deca (let’s say that a Deca-unit is 400 mg) or from 1 "Dianabol -unit" of Dianabol (let’s say that this is 280 mg/week in divided doses every day). If these drugs were as simple in action as Drugs A and B, then the math says that the same result will be obtained regardless of whether one uses one "Deca-unit" of Deca per week, one "Dianabol-unit" of Dianabol per week, or half a unit of each respectively in a stack.

This however is not what happens. Using half a Deca-unit and half a Dianabol-unit per week (say 200 mg/week Deca and 20 mg/day Dianabol) gives better gains than using one unit of either alone. This effect is called synergy and results when there is more than one mechanism of action. The above math remains correct for any given receptor but this is saying that there are more things going on in the body than simply binding to one receptor.

Aside from this and other practical but well-confirmed observations, there is scientific evidence that this is indeed the case.


--------------------------------------------------------------------------------

Scientific Evidence for Multiple Modes of Action

The first thing to consider is whether or not a single mode of action is sufficient to explain all results, as with the simplest case described for Drugs A and B, or whether data is in conflict with such a model.

The equation given earlier allows one, given a measured Kd value, to calculate what percentage of receptors is occupied for a given concentration of drug.

The Kd value for testosterone and the androgen receptor (AR) actually is not known with great precision for humans, but is approximately .44 nmol/L.1 Free testosterone levels in normal men average approximately .07 nmol/L.2,3,4

Contrary to previous statements made by me (although those statements had been made in the scientific literature) this indicates that normal testosterone levels are not sufficient to saturate the AR. The equation given shows that with these values for free testosterone (Tf) and for Kd, one would expect only 14% of ARs to be occupied at any time. Increasing Tf by ten times would improve this to 61% occupancy, which still is not saturated. Increasing twenty times would yield further improvement to 76%. Perhaps this correlates well with the observation that gains improve markedly relative to low dose as one increases amount of testosterone used to 1 gram per week, but going to 2 grams per week offers only a modest further increase.

These results surprise me and are definitely contrary to accepted wisdom. I can only speculate at the moment that those who were trying to determine whether or not receptors are saturated made the mistake of performing the calculation with total testosterone levels instead of Tf. Doing so would lead to that conclusion but is an incorrect method.

I had been going to argue as I had previously that the dose response curve, which extends at least to the 1 gram per week level,5 indicates that there must be more than one mechanism of action, since response increases even past the point of saturation. However these calculations just performed indicate that the dose response curve, through the range that has been studied, is in accord with known values for Kd. This doesn’t prove that there is only one mechanism, but just that one mechanism is not disproven by the dose response curve.

Is there other evidence for multiple mechanisms?

Yes.

First, there are indisputably molecular targets that are not ARs within some cells which bind androgen and give pharmacological response to androgen. These targets may well have (and in some cases are shown to have) quite different binding properties than the AR does. One AAS might be more potent than another at the AR, but less potent at this other target.

Now these targets are not well known or characterized at all, but there is compelling evidence for their existence. First, as discussed above, for any given target (or receptor) drugs acting only at that receptor will behave the same way and differ only in their potencies. Now if all AAS behaved the same way and differed only in their potencies, and had the same ratios of potency regardless of the activity being studied (whether in muscle or skin or nerves, etc.) then this would be consistent with there being only one target or receptor. However, if some AAS are effective in some activities but do nothing in others, while other AAS do have these other activities, then this can’t all be occurring from the same receptor.

Most of the research in this area is rather far removed from bodybuilding, but the principles still apply. Biochemistry is usually much broader than any one specific cell being studied. (For example, most human biochemistry was actually learned originally by study of E. coli and with later research found to be identical in man.) Thus, while we may not care about ductal branching morphogenesis in the developing rat prostate, the fact that a peculiar biochemical mechanism of androgen response occurs here implies that such a mechanism may well exist in things we are interested in, such as bodybuilding. The possibility at least exists.

Speaking of ductal branching morphogenisis in the developing rat prostate,6 here indeed different steroids behave differently. While to the AR testosterone is less potent than DHT, here the reverse relationship was found. Furthermore, methyltrienolone , which is a more potent agonist (activator) of the AR than is DHT, was no more effective than DHT in inducing ductal branching and was less effective than testosterone. This cannot be explained by assuming that aromatization of testosterone to estradiol contributed to the process, because 5a -androstan-3a ,17b -diol (which cannot aromatize) was similarly potent. Thus, there is some target or receptor in these tissues which has different "preferences" (Kd values, and different rank order of potency) than the AR does. Could this also be the case for muscle growth? Perhaps.

Another example is found in the virilization of the mammary gland of female rats.7 The same results are seen here as in the above example of the rat prostate. Testosterone (T) has more activity than DHT does, though at the AR that would not be so.

Differences also are seen in the male accessory glands of the rabbit and rat.8 Testosterone propionate and DHT propionate were found to be equally potent in supporting growth and secretory activity of these glands, but the above-mentioned 5a -androstan-3a ,17b -diol was considerably more potent than these in the prostate but completely ineffective in the epidydimis. Furthermore, use of an antiandrogen (AR blocker) did not affect the function of the epidydimis at all. Thus, the activity of testosterone and DHT in this tissue is not via the AR. Are there muscle-building activities that are not via the AR? If the mechanism exists in one tissue it probably does in others as well.

Here is an activity that is itself of more interest: regulation of lipolysis (fat release) in adipocytes (fat cells).9 T, but not DHT, stimulated catecholamine-induced lipolysis. The findings indicated that T but not DHT induced upregulation of b -adrenergic receptors.

Use of an aromatase inhibitor did not change these results, so conversion to estrogen was not responsible for the difference. If this activity were via the AR, DHT would also have exhibited this effect. Clearly then, something is going on that is not via the AR.

Differential effects of different AAS on human fat cells have also been seen.10 Oxandrolone was most effective in reducing subcutaneous a**ominal fat and visceral fat in obese middle-aged men while weight did not change, as a result of muscle mass increase. Testosterone enanthate gave a small decrease in subcutaneous fat but a slight increase in visceral fat. Nandrolone decanoate also increased visceral fat while decreasing subcutaneous fat. If these activities were via the AR, all three steroids should give the same effects, differing only in potency or the dosage required.

There are some interesting studies on sexual receptivity of female rats. Methyltestosterone , methandrostenolone (Dianabol), nandrolone decanoate, and stanozolol all interfered with sexual receptivity (a different result than seen in human bodybuilders) while testosterone propionate did not.11

In male rats,12,13,14 differential activities are also seen. In intact (non-castrated) male rats, testosterone cypionate , nandrolone decanoate, and methandrostenolone (Dianabol) were all able to support male sexual behavior, while methyltestosterone, stanozolol (Winstrol ), and oxymetholone eliminated male sexual behavior. Again, these results are different than are seen in human bodybuilders. Testosterone cypionate was able to maintain ejaculation in castrated rats, while oxymetholone (Anadrol &#174 was barely able to do so, and stanozolol was unable to do so. This however might have to do with estrogenic activity – use of an aromatase inhibitor was not tried.

Oxandrolone was found incapable of supporting reproductive development in the young male rat.15 Weight of testes, prostate gland, and seminal vesicles were all below controls, and Leydig cells were severely depleted. Again, it was not ruled out that reduced estrogen levels of the oxandrolone-treated animals might have been to blame, so this does not actually prove a non-AR-dependent mechanism for reproductive development. It does indicate that androgens other than testosterone combined with low estrogen levels can result in fertility problems in the rat, and therefore long-term use of nonaromatizing steroids might affect sperm count in the human as well.

Virilizing activities in female rat fetuses also showed a trend of potencies different from trends of binding affinities to the AR.16 The specific test used was measurement of the abridgment of urovaginal septum length: admittedly not so directly relevant for female bodybuilders. The most active AAS was stanozolol, which was more active than methyltestosterone despite having much poor binding affinity to the AR than that steroid .17

In Syrian hamster embryo cells, trenbolone , a more potent agonist of the AR than testosterone, was found unable to transform these cells while testosterone was effective.26 This indicates that the mechanism cannot be simply via the AR.

The AR is not a membrane-associated receptor, but exists within the cell. However, receptors for testosterone have been found in the cell membranes of T cells. The activity of testosterone (increase of amounts of Ca++ within the cell) occurs within seconds (and therefore cannot be via interaction with DNA resulting in increased protein synthesis, since this is a slow process) and was not affected by an AR blocker.18 This effect has also been seen in Sertoli cells.19

Androgen binding receptors have also been found in cell microsomes – these receptors cannot interact with DNA because of their location.20,21,22 Stanozolol has been found to have activity in microsomes that testosterone does not.23,24,25

Lastly, while only stanozolol was tested and therefore we cannot know if there is differential activity between different steroids or not, stanozolol induced a type of skeletal muscle injury that was thought perhaps to stimulate growth, and to induce gene expression by an AR independent mechanism.27 At last, a specific example related to muscle that shows that not all activity is via the AR alone.

We might also speculate that AR upregulation (which has been demonstrated to occur under some conditions (see Androgen Receptor Regulation) is probably not itself mediated by the AR. It would be an unstable mechanism to have the number of ARs increase as a result of increasing numbers of activated ARs. More likely there would be another mechanism.

We may also speculate that different AAS have different effects on nerves, and these effects (being rapid) are not mediated by the AR. E.g., fluoxymesterone, while it binds fairly poorly to the AR, is highly potent in stimulating aggression, and this activity occurs quickly.


--------------------------------------------------------------------------------

Conclusion

What to do with this information? Unfortunately we cannot yet identify how many non-AR-mediated activities there may be. There are I think at least two: activity in microsomes and activities in nerves. There may be more. For example, differentiation of satellite cells of muscle into mature muscle cells might be a non-AR mediated activity.

The practical application of this is that one should not use only a steroid which is good at some things but not others. Examples of this would be Deca and Primobolan (good agonists of the AR but this is not sufficient to make them outstanding anabolics) and Anadrol® and Dianabol, which are weaker agonists of the AR yet effective anabolics. Combining drugs of one type with the other is synergistic. It may also be that testosterone and trenbolone are synergistic – trenbolone is much more potent at the AR but (as seen with the Syrian hamster cells) testosterone has at least one activity that trenbolone does not. Winstrol has metabolic properties that testosterone lacks.

Is there a reason to use both Dianabol and Anadrol® together? Does one have one non-AR mediated activity which the other lacks? I think not, although Anadrol® does seem to have progestogenic activity which Dianabol does not. In any case I don’t know anyone who likes to combine these drugs.

Right now I would say that all bases are covered with testosterone plus trenbolone plus (Dianabol or Anadrol&#174 plus Winstrol. I am not sure that there is no overlap: perhaps the activities of testosterone are covered by the other three.

I hope that future careful observations of results obtained in bodybuilding will allow a more precise answer to this question in the future

[cantspeak]

One rather key issue to usage of anabolic /androgenic steroids (AAS) is how one chooses which to use, or which combination to use, and indeed, why combinations might be superior to comparable amounts of single steroids. The issue of combining AAS for most efficient muscle gain is one that has been entirely neglected in the medical literature, since acquisition of muscle is not considered of therapeutic necessity, and observations by bodybuilders have unfortunately generally not been made in a systematic manner. I cannot yet give definitive and complete answers on this matter, but some things are clear at this point, and general support for the principle of synergy can be found in some scientific studies.


--------------------------------------------------------------------------------

Pharmacology in the Simplest Case

First, let us consider the case of the simplest kind of drug. This drug would act in only one way, and would do so by binding to a receptor and activating it. The amount of activity performed by that type of receptor would be directly proportional to the number of receptors that bound the drug. Nothing else of any kind would be going on with this drug.

There might also be similar drugs which worked the exact same way, binding to the same receptor. The only ways in which these drugs could differ from the practical point of view are in pharmacokinetics (how fast each drug enters and clears the body) and how potent each drug is. The latter term is one that may easily be misunderstood due to common usage differing from scientific usage. Potency refers to how little of a drug is required to give a defined amount of effect. For example, if one may obtain the desired therapeutic effect in 50% of subjects with 1 mg/day of Drug A or 100 mg/day of Drug B, then Drug A is 100 times more potent.

This does not mean that Drug A is necessarily better! One can get the same effect from Drug B simply by using 100 times as much. It might be the case that Drug B might be preferable despite the higher required dose: for example, if Drug A leaves the body too quickly or too slowly, or has more toxicity for the same therapeutic effect. It means only that in comparing the drugs, to compare them equally, one must compare the effects of 1 unit of Drug A to 100 unit of Drug B.

To understand this a little more, unfortunately we have to use a little math. One could skip over the math if desired and just look at the conclusions which follow fairly easily from the numbers calculated.

Drugs and receptors interact with each other according to a simple equation:

(conc. of drug) (conc. receptor)
Kd = -------------------------------------
(conc. of drug « receptor)

where (conc. of drug « receptor) is the concentration or amount per volume of receptors that have drug bound to them, and (conc. of drug) and (conc. of receptor) refer to the concentrations of free drug and receptor respectively.

This number Kd is a constant (always the same) for any given drug, but will vary between drugs of different potencies. This fact allows us to calculate the percentage of receptors occupied if we know Kd and the amount of drug.

Kd will be expressed in units of concentration, for example, 1 nanogram per liter. More potent drugs have lower Kd values. In our comparison of Drugs A and B where A was 100 times more potent, if Drug A had a Kd value with the receptor of 1 ng/L, then drug B would have a Kd of 100 ng/L: you would need 100 times more of Drug B to get the same effect.

What would happen therapeutically if you "stacked" Drug A and Drug B?

You can play with the math and you will find that using blends of A and B, where one keeps in mind that B is 100 times less potent and therefore uses 100 mg of it for each unit of A it replaces, that one gets the exact same result regardless of the stacking. Let’s say that Drug A comes in 1 mg tablets and Drug B comes in 100 mg tablets. Each tablet therefore gives the same effect. In the case of the simplest type of drug such as these two drugs, the effect is identical whether one uses 10 tabs of A, 10 tabs of B, or 5 tabs of each. The same number of receptors are occupied regardless and the effect is the same.

Therefore, stacking these drugs makes about as much sense as stacking two brands of aspirin or two brands of coffee. It is okay if one happens to have both available, but there is no reason to go out and buy the second brand in the hopes that stacking it will give more of a caffeine buzz, or more pain relief.

The mixing might make sense if there were a pharmacokinetic difference: perhaps one of the brands of aspirin is time-released and you want both an instant hit for immediate pain relief as well as sustained action. (The sustained action though could be obtained with only the regular brand, simply by taking small amounts frequently.)



--------------------------------------------------------------------------------

Application to AAS

Now the obvious question here is, Is the same type of drug response true with AAS, or are more complex things going on? Let’s say that, used alone, the same effect is obtained from 1 "Deca -unit" of Deca (let’s say that a Deca-unit is 400 mg) or from 1 "Dianabol -unit" of Dianabol (let’s say that this is 280 mg/week in divided doses every day). If these drugs were as simple in action as Drugs A and B, then the math says that the same result will be obtained regardless of whether one uses one "Deca-unit" of Deca per week, one "Dianabol-unit" of Dianabol per week, or half a unit of each respectively in a stack.

This however is not what happens. Using half a Deca-unit and half a Dianabol-unit per week (say 200 mg/week Deca and 20 mg/day Dianabol) gives better gains than using one unit of either alone. This effect is called synergy and results when there is more than one mechanism of action. The above math remains correct for any given receptor but this is saying that there are more things going on in the body than simply binding to one receptor.

Aside from this and other practical but well-confirmed observations, there is scientific evidence that this is indeed the case.


--------------------------------------------------------------------------------

Scientific Evidence for Multiple Modes of Action

The first thing to consider is whether or not a single mode of action is sufficient to explain all results, as with the simplest case described for Drugs A and B, or whether data is in conflict with such a model.

The equation given earlier allows one, given a measured Kd value, to calculate what percentage of receptors is occupied for a given concentration of drug.

The Kd value for testosterone and the androgen receptor (AR) actually is not known with great precision for humans, but is approximately .44 nmol/L.1 Free testosterone levels in normal men average approximately .07 nmol/L.2,3,4

Contrary to previous statements made by me (although those statements had been made in the scientific literature) this indicates that normal testosterone levels are not sufficient to saturate the AR. The equation given shows that with these values for free testosterone (Tf) and for Kd, one would expect only 14% of ARs to be occupied at any time. Increasing Tf by ten times would improve this to 61% occupancy, which still is not saturated. Increasing twenty times would yield further improvement to 76%. Perhaps this correlates well with the observation that gains improve markedly relative to low dose as one increases amount of testosterone used to 1 gram per week, but going to 2 grams per week offers only a modest further increase.

These results surprise me and are definitely contrary to accepted wisdom. I can only speculate at the moment that those who were trying to determine whether or not receptors are saturated made the mistake of performing the calculation with total testosterone levels instead of Tf. Doing so would lead to that conclusion but is an incorrect method.

I had been going to argue as I had previously that the dose response curve, which extends at least to the 1 gram per week level,5 indicates that there must be more than one mechanism of action, since response increases even past the point of saturation. However these calculations just performed indicate that the dose response curve, through the range that has been studied, is in accord with known values for Kd. This doesn’t prove that there is only one mechanism, but just that one mechanism is not disproven by the dose response curve.

Is there other evidence for multiple mechanisms?

Yes.

First, there are indisputably molecular targets that are not ARs within some cells which bind androgen and give pharmacological response to androgen. These targets may well have (and in some cases are shown to have) quite different binding properties than the AR does. One AAS might be more potent than another at the AR, but less potent at this other target.

Now these targets are not well known or characterized at all, but there is compelling evidence for their existence. First, as discussed above, for any given target (or receptor) drugs acting only at that receptor will behave the same way and differ only in their potencies. Now if all AAS behaved the same way and differed only in their potencies, and had the same ratios of potency regardless of the activity being studied (whether in muscle or skin or nerves, etc.) then this would be consistent with there being only one target or receptor. However, if some AAS are effective in some activities but do nothing in others, while other AAS do have these other activities, then this can’t all be occurring from the same receptor.

Most of the research in this area is rather far removed from bodybuilding, but the principles still apply. Biochemistry is usually much broader than any one specific cell being studied. (For example, most human biochemistry was actually learned originally by study of E. coli and with later research found to be identical in man.) Thus, while we may not care about ductal branching morphogenesis in the developing rat prostate, the fact that a peculiar biochemical mechanism of androgen response occurs here implies that such a mechanism may well exist in things we are interested in, such as bodybuilding. The possibility at least exists.

Speaking of ductal branching morphogenisis in the developing rat prostate,6 here indeed different steroids behave differently. While to the AR testosterone is less potent than DHT, here the reverse relationship was found. Furthermore, methyltrienolone , which is a more potent agonist (activator) of the AR than is DHT, was no more effective than DHT in inducing ductal branching and was less effective than testosterone. This cannot be explained by assuming that aromatization of testosterone to estradiol contributed to the process, because 5a -androstan-3a ,17b -diol (which cannot aromatize) was similarly potent. Thus, there is some target or receptor in these tissues which has different "preferences" (Kd values, and different rank order of potency) than the AR does. Could this also be the case for muscle growth? Perhaps.

Another example is found in the virilization of the mammary gland of female rats.7 The same results are seen here as in the above example of the rat prostate. Testosterone (T) has more activity than DHT does, though at the AR that would not be so.

Differences also are seen in the male accessory glands of the rabbit and rat.8 Testosterone propionate and DHT propionate were found to be equally potent in supporting growth and secretory activity of these glands, but the above-mentioned 5a -androstan-3a ,17b -diol was considerably more potent than these in the prostate but completely ineffective in the epidydimis. Furthermore, use of an antiandrogen (AR blocker) did not affect the function of the epidydimis at all. Thus, the activity of testosterone and DHT in this tissue is not via the AR. Are there muscle-building activities that are not via the AR? If the mechanism exists in one tissue it probably does in others as well.

Here is an activity that is itself of more interest: regulation of lipolysis (fat release) in adipocytes (fat cells).9 T, but not DHT, stimulated catecholamine-induced lipolysis. The findings indicated that T but not DHT induced upregulation of b -adrenergic receptors.

Use of an aromatase inhibitor did not change these results, so conversion to estrogen was not responsible for the difference. If this activity were via the AR, DHT would also have exhibited this effect. Clearly then, something is going on that is not via the AR.

Differential effects of different AAS on human fat cells have also been seen.10 Oxandrolone was most effective in reducing subcutaneous a**ominal fat and visceral fat in obese middle-aged men while weight did not change, as a result of muscle mass increase. Testosterone enanthate gave a small decrease in subcutaneous fat but a slight increase in visceral fat. Nandrolone decanoate also increased visceral fat while decreasing subcutaneous fat. If these activities were via the AR, all three steroids should give the same effects, differing only in potency or the dosage required.

There are some interesting studies on sexual receptivity of female rats. Methyltestosterone , methandrostenolone (Dianabol), nandrolone decanoate, and stanozolol all interfered with sexual receptivity (a different result than seen in human bodybuilders) while testosterone propionate did not.11

In male rats,12,13,14 differential activities are also seen. In intact (non-castrated) male rats, testosterone cypionate , nandrolone decanoate, and methandrostenolone (Dianabol) were all able to support male sexual behavior, while methyltestosterone, stanozolol (Winstrol ), and oxymetholone eliminated male sexual behavior. Again, these results are different than are seen in human bodybuilders. Testosterone cypionate was able to maintain ejaculation in castrated rats, while oxymetholone (Anadrol &#174 was barely able to do so, and stanozolol was unable to do so. This however might have to do with estrogenic activity – use of an aromatase inhibitor was not tried.

Oxandrolone was found incapable of supporting reproductive development in the young male rat.15 Weight of testes, prostate gland, and seminal vesicles were all below controls, and Leydig cells were severely depleted. Again, it was not ruled out that reduced estrogen levels of the oxandrolone-treated animals might have been to blame, so this does not actually prove a non-AR-dependent mechanism for reproductive development. It does indicate that androgens other than testosterone combined with low estrogen levels can result in fertility problems in the rat, and therefore long-term use of nonaromatizing steroids might affect sperm count in the human as well.

Virilizing activities in female rat fetuses also showed a trend of potencies different from trends of binding affinities to the AR.16 The specific test used was measurement of the abridgment of urovaginal septum length: admittedly not so directly relevant for female bodybuilders. The most active AAS was stanozolol, which was more active than methyltestosterone despite having much poor binding affinity to the AR than that steroid .17

In Syrian hamster embryo cells, trenbolone , a more potent agonist of the AR than testosterone, was found unable to transform these cells while testosterone was effective.26 This indicates that the mechanism cannot be simply via the AR.

The AR is not a membrane-associated receptor, but exists within the cell. However, receptors for testosterone have been found in the cell membranes of T cells. The activity of testosterone (increase of amounts of Ca++ within the cell) occurs within seconds (and therefore cannot be via interaction with DNA resulting in increased protein synthesis, since this is a slow process) and was not affected by an AR blocker.18 This effect has also been seen in Sertoli cells.19

Androgen binding receptors have also been found in cell microsomes – these receptors cannot interact with DNA because of their location.20,21,22 Stanozolol has been found to have activity in microsomes that testosterone does not.23,24,25

Lastly, while only stanozolol was tested and therefore we cannot know if there is differential activity between different steroids or not, stanozolol induced a type of skeletal muscle injury that was thought perhaps to stimulate growth, and to induce gene expression by an AR independent mechanism.27 At last, a specific example related to muscle that shows that not all activity is via the AR alone.

We might also speculate that AR upregulation (which has been demonstrated to occur under some conditions (see Androgen Receptor Regulation) is probably not itself mediated by the AR. It would be an unstable mechanism to have the number of ARs increase as a result of increasing numbers of activated ARs. More likely there would be another mechanism.

We may also speculate that different AAS have different effects on nerves, and these effects (being rapid) are not mediated by the AR. E.g., fluoxymesterone, while it binds fairly poorly to the AR, is highly potent in stimulating aggression, and this activity occurs quickly.


--------------------------------------------------------------------------------

Conclusion

What to do with this information? Unfortunately we cannot yet identify how many non-AR-mediated activities there may be. There are I think at least two: activity in microsomes and activities in nerves. There may be more. For example, differentiation of satellite cells of muscle into mature muscle cells might be a non-AR mediated activity.

The practical application of this is that one should not use only a steroid which is good at some things but not others. Examples of this would be Deca and Primobolan (good agonists of the AR but this is not sufficient to make them outstanding anabolics) and Anadrol® and Dianabol, which are weaker agonists of the AR yet effective anabolics. Combining drugs of one type with the other is synergistic. It may also be that testosterone and trenbolone are synergistic – trenbolone is much more potent at the AR but (as seen with the Syrian hamster cells) testosterone has at least one activity that trenbolone does not. Winstrol has metabolic properties that testosterone lacks.

Is there a reason to use both Dianabol and Anadrol® together? Does one have one non-AR mediated activity which the other lacks? I think not, although Anadrol® does seem to have progestogenic activity which Dianabol does not. In any case I don’t know anyone who likes to combine these drugs.

Right now I would say that all bases are covered with testosterone plus trenbolone plus (Dianabol or Anadrol&#174 plus Winstrol. I am not sure that there is no overlap: perhaps the activities of testosterone are covered by the other three.

I hope that future careful observations of results obtained in bodybuilding will allow a more precise answer to this question in the future

[AnabolicAndre]

thats so much information. Helpful though thankyou.

[oswaldosalcedo]

The 17AA steroids don’t bind to the A.R and promote anabolism via other mechanisms of action.

then, they do not bind or low bind to the G.R either.
you have given me the key for my theory.

[Dr James Daemon]

Its a bloody long piece, but it has to be to lay the conceptual basis for why relative concentration tends to go against conventional methods of stacking drugs.
Please (if you can!) read the whole thing, use the glossary of terms, and enjoy!

[doctadank]

Tbol is garbage.

As to your original question, that for which the thread was started, i believe in synergistic stacking: That which takes into account not only the 'different families' of AAS.. but also the individual's body composition/body type (somatotype); natural hormone levels; predispositions (for sides; gynaeco; MPB etc.)

For me, tho i will may again list my cycles online i will state however that, i run dht-based cycles: 1-2 dht-based compounds (because i respond better to DHT) + TRT + a majorly anabolic compound

...maybe a non-androgen-based anabolic as well

e.g.

Weeks 1-16 masteron (prop ester) 100 mg ED
Weeks 1-8; 9-16 Winstrol 100 mg ED
Weeks 1-10 test-prop 50 mg ED
Weeks 1-10 tren -ace 100 mg ED
Weeks 1-22** Insulin pwo 10 IUs

** Insulin use extends to PCT (insulin being the non-androgen-derived anabolic as mentioned above)

Narkissos

i aswell agree with narkossis.
ive ran tbol 2x at 60mgday and then at 80-100mg day
wasnt effective for me to notice a diff in my tren/prop cycle n eways

[rock75]

whole cycle - insulin , humalog - PWO 10iu

the gh is out of the question for me at that dose is too pricey.

IMO - INSULIN USE SHOULD ONLY BE USED BY THOSE EXPERIENCED**

too much, too little - diabetic shock and bye-bye - you could possibly kill yourself

[marcus300]

IMO - INSULIN USE SHOULD ONLY BE USED BY THOSE EXPERIENCED**

too much, too little - diabetic shock and bye-bye - you could possibly kill yourself

correct

[MMA]

great info in this thread. but it leads me to a question - i was considering doing an all test cycle. for one reason or another, i couldn't use any of my other favorites

- deca - (detection time too long)

- EQ - messes with GABA receptors, causes me extreme anxiety

- winny - joint problems are bad enough already

- tren - kills my cardio - HORRIBLE in my sport.

- no orals whatsoever - i'm already on some fairly liver toxic medication

whats left that combines well with Test that's good for my sport?

[guest589745]

great info in this thread. but it leads me to a question - i was considering doing an all test cycle. for one reason or another, i couldn't use any of my other favorites

- deca - (detection time too long)

- EQ - messes with GABA receptors, causes me extreme anxiety

- winny - joint problems are bad enough already

- tren - kills my cardio - HORRIBLE in my sport.

- no orals whatsoever - i'm already on some fairly liver toxic medication

whats left that combines well with Test that's good for my sport?

Masteron might cause similar problems as Winny being a DHT and Im not sure if the detection time would be a problem for you, Id have to double check on that but, thast about all I can think of.

Well, maybe Reforvit?

Give IGF-1 a shot? HGH?

what are you actually on that is liver toxic?

Is Nandrolne propionate still a long detection time like decanoate? If not, that could work.

[one8nine]

great info in this thread. but it leads me to a question - i was considering doing an all test cycle. for one reason or another, i couldn't use any of my other favorites

- deca - (detection time too long)

- EQ - messes with GABA receptors, causes me extreme anxiety

- winny - joint problems are bad enough already

- tren - kills my cardio - HORRIBLE in my sport.

- no orals whatsoever - i'm already on some fairly liver toxic medication

whats left that combines well with Test that's good for my sport?

you could try to convert dbol or anadrol into an injectable

i like masteron

maybe some proviron just to give your test a little bit more kick, and maybe some epo with that?

[one8nine]

OSWALDOSALCEDO how does the tren oral work? is it an acetate?...by the way i'm also using win/dbol in 75/125 respectively mon-fri(training days) with EQ.

thats probabl a terrible idea

[rock75]

Given to me from a respected No Bull member... All though he has suggested doing this through a short cycle the principal is still the same in longer cycles. No matter the case, by the end your are not terminally shut down and will recover a lot easier/faster.

Try doing a cycle where you do high androgens for the first third of the cycle then switch to androgenic /anabolic gear for 2nd third of cycle then last third of cycle do all anabolic.

Something like this-

week 1&2 Sustanon , Test Enanthate , Deca
week 3&4 Primobolan , Test Propionate , Tren
week 5&6 Winstrol , Durabolin (not deca) any fast acting anabolic

this will be the basis of my next cycle, whenever that is

[vitor]

Given to me from a respected No Bull member... All though he has suggested doing this through a short cycle the principal is still the same in longer cycles. No matter the case, by the end your are not terminally shut down and will recover a lot easier/faster.

Try doing a cycle where you do high androgens for the first third of the cycle then switch to androgenic /anabolic gear for 2nd third of cycle then last third of cycle do all anabolic.

Something like this-

week 1&2 Sustanon , Test Enanthate , Deca
week 3&4 Primobolan , Test Propionate , Tren
week 5&6 Winstrol , Durabolin (not deca) any fast acting anabolic

this will be the basis of my next cycle, whenever that is

This way of cycling is very popular where I am from.

The idea is to use the heavy(supressive) anabolics like test and tren early in the cycle, and then swithch to drugs which has better anabolic to supressive ratio, like Primo, anavar , Halo, winny or masteron for the last 3-4 weeks in the cycle, to allow for a faster recovery.

[Swifto]

This way of cycling is very popular where I am from.

The idea is to use the heavy(supressive) anabolics like test and tren early in the cycle, and then swithch to drugs which has better anabolic to supressive ratio, like Primo, anavar, Halo, winny or masteron for the last 3-4 weeks in the cycle, to allow for a faster recovery.

Not sure if you have ever read any of Ross's new ideas. He suggests stopping the more suppressive androgens 4-5 weeks prior to the cycling ending, whilst carrying on with the not so suppressive androgens. There isnt an scientific evidence to suggest the pituitary will start up again and resume hormone output after the cessation of the more suppressive androgens, but I'm trying it next cycle! Got to experiemnt of you'll never know IMO.

An example cycle would be:

wk 1-8 Test Prop 50mg/ED
wk 1-10 Tbol 60-80mg/ED
wk 1-12 Primo 600-800mg/wk
wk 1-PCT 25-50mg/ED

Thats the next cycle I'll be doing.

[vitor]

Not sure if you have ever read any of Ross's new ideas. He suggests stopping the more suppressive androgens 4-5 weeks prior to the cycling ending, whilst carrying on with the not so suppressive androgens. There isnt an scientific evidence to suggest the pituitary will start up again and resume hormone output after the cessation of the more suppressive androgens, but I'm trying it next cycle! Got to experiemnt of you'll never know IMO.

An example cycle would be:

wk 1-8 Test Prop 50mg/ED
wk 1-10 Tbol 60-80mg/ED
wk 1-12 Primo 600-800mg/wk
wk 1-PCT 25-50mg/ED

Thats the next cycle I'll be doing.

Yeah, this is what I meant.

Youre right, there is no evidence that the pituitary will start up again b/f the whole cycle is over. But it sounds good in theory. I know people who swears by this to.

One importent thing here is to use an AI to keep estrogen "low". Especially when you use and are coming off the Prop(which aromatize), as estrogen will inhibit the Pituitary. 25 mgs ed of Proviron might not be sufficent to do this...

If you try it let us know how it goes...

[taiboxa]

i would ljust like to add that..

Tren + halo was FUN and when i added deca /eq to it i got nice joint therapy and veins

[MMA]

Masteron might cause similar problems as Winny being a DHT and Im not sure if the detection time would be a problem for you, Id have to double check on that but, thast about all I can think of.

Well, maybe Reforvit?

Give IGF-1 a shot? HGH?

what are you actually on that is liver toxic?

Is Nandrolne propionate still a long detection time like decanoate? If not, that could work.

so much great info by knowledgable bros on this thread, i had to bring it back.

i was already planning on adding GH/IGF/sln/PGF2a and other items to this stack, i was just commenting on my AS program.

my liver toxic medication is wellbutrin, and it is such an incredible performance enhancer for me, i would rather use it than any oral streroid.

a little background on ADD medications like wellbutrin, and other nootropic "smart drugs" for yor brain.

they are the "dirty little secret" of many elite high schools - as much as 80% of the student population at some are "diagnosed" with ADD. this allows them to get drugs that are basicly "steroids for your brain". you can take this stuff and study dense german philosophy textbooks for 16 hours straight.


my first tiny "starter dose" of wellbutrin ended up with me pulling my car over to a dumpster and completely cleaning and organizing it for hours. i have intense focus and concentration and discipline and i have never b4 posessed.

it is a huge edge in my jiu jitsu training because i can watch HOURS of training tape every day, and apply it to my training the same night. i can visualize and memorize moves at as level i never could b4.

i think it speeds up my reflexes a bit too.

[MMA]

i'm going to check my liver values, and if they're not too bad, i'm going to run anavar 2 weeks b4 a fight, swithch off to halo for the last week, and use mibolerone and some other goodiers on fight night.

hopefully, i'll be able to handle 2 weeks of orals at a a time, and still keep my wellbutrin.

[alwayson]

I would like to see Anthony Robert's input on this whole topic of synergistic stacking

[alwayson]

unless it is addressed in his book....if it is...someone let me know, I might buy it

[MMA]

alright, with additional research, my cycle looks to be NPP/test/masteron , with var or halo added in near fight time.

NPP for injury resistance, collagen synthesis, good basic anabolic , without the crazy detection times of deca .

masteron - becuase of it's affinity for the AR receptor, the synergystic stacking noted above, and its history of successful use with athletes.

test - because test is best

var to add a little extra strength to my already massive frame. later, switching off to halo for even more.

mibolerone , fight night only, to turn me into a rampaging BEAST!

sound good to the experts?

[guest589745]

Looks good, hit it up.

[MMA]

alright, with additional research, my cycle looks to be NPP/test/masteron , with var or halo added in near fight time.

NPP for injury resistance, collagen synthesis, good basic anabolic , without the crazy detection times of deca .

masteron - becuase of it's affinity for the AR receptor, the synergystic stacking noted above, and its history of successful use with athletes.

test - because test is best

var to add a little extra strength to my already massive frame. later, switching off to halo for even more.

mibolerone , fight night only, to turn me into a rampaging BEAST!

sound good to the experts?

tweaked with a little more research.

no NPP - detection time still too long. maybe i could work something with nandrolone base in a cyclodextrin sunlingual.

and i'm adding a VERY low dose of furazabol throughout, for cardiovascular health.

[Property of Steroid.com]

I would like to see Anthony Robert's input on this whole topic of synergistic stacking

http://www.anthony-roberts.com/designing_cycle.html

[BajanBastard]

tweaked with a little more research.

no NPP - detection time still too long. maybe i could work something with nandrolone base in a cyclodextrin sunlingual.

and i'm adding a VERY low dose of furazabol throughout, for cardiovascular health.

How much furazabol will you be using exactly?

[guest589745]

and i'm adding a VERY low dose of furazabol throughout, for cardiovascular health.

furazabol can be beneficial for cardiovascular health? I thought 19nors were bad on cholesterol ?

[BajanBastard]

furazabol can be beneficial for cardiovascular health? I thought 19nors were bad on cholesterol ?

Furazabol is not a 19 NOR, it’s a DHT derivative.

Looks like winny in structure.


Stanozolol





Furazabol





3 mg ED has been shown to the lower LDL and raise HDL.

[alwayson]

http://www.anthony-roberts.com/designing_cycle.html

What kind of drug is primo according to your 3 categories, and what kind of stack would be best for it?

[guest589745]

I need to find some of that!

[guest589745]

I think the thread shouldve been titled:

"Synergistic stacking................the best way"

[BajanBastard]

What kind of drug is primo according to your 3 categories, and what kind of stack would be best for it?

Primo is a DHT based drug. I'll never use it but if i was to get 50 grams free i would stack it with trenbolone , stanozolol and a TRT dose of testosterone .