PCT: A Clinician's View - PRIMER

Originally Posted by dinoiii

PCT: A Clinician's View - PRIMER

Dana Houser
MD, MHSA candidate

Author’s Note: The aforementioned individual assumes NO responsibility for the information presented herein. While the information presented has dual source: medical and scientific sources referenced at the conclusion of the series and additionally verified values from actual patient labs (verified by Quest Diagnostics), it is NOT to be assumed replacement for your own physician’s advisement nor should it act as replacement for such abilities of the individual as having their own serum studies drawn. This information is believed by the author to be accurate and reliable, and with such connotation, to be presented for the sole purpose of interested parties to address the information to follow with their own physician.

The opinions expressed by the author do not necessarily represent the opinions or the views of Chris Catchis, nor Discount Anabolics. Nor should the information herein be used to treat or to prevent any medical condition unless it is used with the full knowledge, compliance, and agreement of an examining physician or other licensed health care professional assuming that role. Readers are, once again, strongly advised to seek the advice of their personal health care professional(s) and discussing the information contained in this informational series BEFORE proceeding with ANY changes in ANY health care program.

The author reserves all rights to the series of articles that follow. No part of this work may be reproduced or transmitted in ANY form OR by ANY means, electronic OR mechanical, INCLUDING photocopying and recording, or by any information storage or retrieval system, EXCEPT for those wishing to quote brief passages or recommendations in connection with a review.





This information is only a sampling of a book to be released next year.

Great info

Originally Posted by dinoiii

Series to Follow (Expected Drop Dates have changed)

Part I: PCT Demystified

Part II: Post-Cycle Supplements: In Theory

Part III: Post-Cycle Supplements: In Practice

Part IV: Post-Cycle Pharmaceutics: In Theory

Part V: Post-Cycle Pharmaceutics: In Practice

Part VI: Post-Cycle Lifestyle Modification

Part VII: Individualizing What We’ve Learned

.....

Originally Posted by dinoiii

PCT: A Clinician's View PART I
PCT Demystified!

Dana Houser
MD, MHSA candidate

Author's Note: If you have not done so, please observe the PCT: A Clinican's View Primer thread before continuing on at:
http://www.discountanabolics.com/for...ead.php?t=2012

Introduction

As with many of the “truths” preached in all facets of life – there are always origins. Like a game of “telephone” played as a child, we hope the initial message doesn’t come out all jumbled by the time it is sent back to the message starter. Even then, the question isn’t so much how jumbled the message has become, as it is more likely a question of how jumbled the message was to begin with. This very idea governs this discussion as more accurately a game of dominoes versus telephone – where one party begins to preach the either half-truth or entire fallacy and everyone thereafter simply follows suit because it is simply now said to be SO. Somewhere along the annals of bodybuilding time, this game of dominoes reared its ugly head in consideration of PCT (post-cycle therapy). I will not claim to know the origin and personally, I don’t care.

While PCT should not be something so mystic in nature, it has gained that reputation because everyone seemingly has their own viewpoint on what should be considered standard practice when designing such regimes. This is likely for no better reason than as already stated, it is said to be SO. Unfortunately, this is one area in which “standards” have been unable to be set and offers serious concern as long-term health consequences can result through the inappropriate actions of those partaking in self-medication and supplementation. Well, of course that is, until NOW.

Everyone in the medical profession and government alike tend to close their eyes and pretend that this kind of topic need not be addressed and abolishing the use of every anabolic would be more justified (while potentially more damaging substances – cigarettes and alcohol remain legalized due to their highly economic nature and this alone). The truth is that number one, AS cycles and accompanying PCT is a very real practice that cannot simply go unrecognized (as may be evidenced by simply going to your bodybuilding site of choice and perusing the multitudes of both questions and answers supplied by countless masses on the accompanying forum) and number two, complete abolishment has the potential to make situations worse (case-in-point: bodybuilders of the pre-AS Control Act of 1990 versus the very beast-like bodybuilders of today’s post-AS Control Act of 1990 + 2004 era).

With development of new, not-well thought out compounds, mail-order dangers of potentially lethal substances, and the use of veterinary equivalents, the truth is AS use could never be fully controlled. Unfortunately, the essential behavior in regards to alteration of the homeostatic environment known as the human body is one that could hold dire consequence and the medical establishment and government would be better justified in realms of creating education versus abolishment.

The essential purpose of these articles is to guide either the health care practitioner as well as individuals having already taken the plunge into introduction of exogenous anabolic substances into their bodies on how to design a SAFE way to come off cycle TOGETHER. Hopefully, in alleviation of the consequences I alluded to in the aforementioned paragraphs. ALL aspects of this topic will be explored at great depth watching all of the evidence-based literature (or lack thereof) not only reviewed as well as seeing it played out in practice. We will also do a lot of dispelling myths, as continued via domino fashion. The rationale for writing such a series on such a bastardized “dirty” topic in medicine today is to avoid potentially life-modifying, or potentially worse, life-ending consequence.

The Harshest of Critics

One of the harshest criticisms given to such an article set like this is that I have never used “AS” myself. This is in fact true, by legal definition! I would NOT have considered myself serious enough, nor even remotely close to my non-anabolic potential pre-1990 to consider it. After that time frame, the various modes of obtaining them seemed to not favor future goals should anything had gone awry. Oh yeah, and there was also that whole age thing that didn’t work in my favor at the time either – I was thirteen (a far cry from the 25 year old age limit I tend to preach).

[Author’s note: I have, in fact, used many items considered “PH’s / PS’s” at the time as many are aware. Again, it may simply come down to a matter of definition.]

I combat that potential dagger with the essence of having the opportunity to have lived vicariously through many clients that have used AS and witnessed various hormonal response – VERIFIED THROUGH LAB REPORT! That latter statement is something most “authorities” cannot preach even about their own precious cycles that somehow make them the authority. I personally think that the data chroniclizing what happens to one person tells us NOTHING (as one person’s hormonal response proves to neither be synonymous nor homologous with constancy across all hormonal responses); a better picture ONLY truly becomes apparent when numerous individuals are tested seeing how various serum studies pan out.

The next time you are confronted by someone who preaches that they simply sought out any potential hypogonadal symptoms as their hormonal indication something was wrong and based their use of various substances to prevent them on those potential sides...I ask you to step away from their advice. In fact, 86% of hormonal decline experienced by users while in either the peri-cycle or post-cycle time frame do NOT show up clinically. In fact, the biggest error would be to not run labs to tease out these discrepancies in the first place, which unfortunately is more commonplace than is given credit.

Our Journey

The task at hand appears quite daunting at first look. After all, I never said covering all topics in a broad-based topic like PCT would be easy. Interestingly enough, individuals have tried to cover this topic in one short-piece; we’ll now together embark on a seven part series that includes, yet still only scratches the surface, of the following subject areas:

Part I: PCT Demystified
Part II: Post-Cycle Supplements: In Theory
Part III: Post-Cycle Supplements: In Practice
Part IV: Post-Cycle Pharmaceutics: In Theory
Part V: Post-Cycle Pharmaceutics: In Practice
Part VI: Post-Cycle Lifestyle Modification
Part VII: Individualizing what we’ve Learned

Without further adieu, we will jump head-first into our opening on pharmaceutics and dietary supplements purported to offer benefit in the PCT time frame, which as noted will continue to span four additional parts.

...

Concurrent Agents: Pharmaceutics & Supplements

In debating what topic to start with – it literally jumped out at me that concurrents would get first bid as they are most often talked about in lieu of lifestyle modifications that should NOT be considered in ANY way less important. I can’t help but assume this to be in line with the ideology that many hold on how much easier it is to simply ingest a pill in hopes to correct all ailments. Perhaps, this is one theme that has emerged from the prototypical doctor’s office visit. Without gaining that little white (or various other colors) slip to go fill up at the local pharmacy, we don’t feel the visit to the doctor was worth the price of admission.

It may be more accurate to say that our avoidance of lifestyle responsibilities and near-total reliance upon drugs to deal with the state of affairs associated with PCT has been an ultimate result of some fundamental assumptions of Western – especially American – culture. Perhaps the problem is not them (government and pharmaceutics) after all, but us – all of us.

I believe both pharmaceutics AND dietary supplements hold roles in the ideal post-cycle run, unfortunately both are not necessarily always addressed in an unbiased – non-vested interest sort of way. People are naturally skeptical when someone makes extravagant claims for healing methods or healing substances – dietary supplements or otherwise. This is not necessarily an unwarranted rationale in many instances, but the converse is true of many others.

The dominant approach in health care in our culture is based on the notion of specific diseases and specific medications for specific diseases. I have joked in the past about how we actually create diseases based on medications we have FIRST developed. This isn’t necessarily as much a joke as its initial intention – and I truly believe this more and more as I get further into my study of allopathic medicine! With today’s abundance of new nutritional supplements and the accompanying promotional literature glowing with enthusiastic claims, separating fact from fiction has become about as difficult as it has with pharmaceutics that sat in the front seat as essential predecessors.

Perhaps, My Own Horn-Tooting?

The “usual suspects” (Nolva, Arimidex, AT, ATD, even clomiphene and the most poorly understood, hCG) will be explored, exaggerated dosing protocols, the potential detriment of various interactions and why it is inappropriate for any company to claim to develop the end-all, be-all PCT supplement and how these individual agents will and have affected various blood labs. You will be a student of endocrinology, perhaps unbeknownst to you for at least this seven part series. You will learn things of absolute cutting edge mentality – never before written in this industry, I assure you. I have never dressed to NOT impress. Heck, I may be the last domino standing! Stay tuned...we’re just getting started!

...

Originally Posted by dinoiii

PCT: A Clinician's View Part II:
Post-Cycle Supplements - IN THEORY




Introduction

The three endogenous steroids of primary importance during the PCT time frame are testosterone, dihydrotestosterone, and estradiol as many “authorities” have likely kept you well informed. And it is true that from a quantitative standpoint, the most important androgen is in fact testosterone – BUT this should NOT detract in any way from the importance that is regaining control of the others. Without an understanding of exactly what is going on in your body, and why certain compounds help to correct the situation, choosing the right post cycle program can pose itself as quite the conundrum. This is namely due, in large part, to all the “wonder” recommendations floating about.

While your head has thrown into tail spin getting caught up on the various recommendations – reading any and every thing you can get your hands on, you feel you have arrived at the appropriate conclusion of what might be the very best post cycle options. But – we both know what you’re thinking! Have I made the right decision? Could I have read more? And, if you are like many I have seen in the past – is this the best subset of supplements/pharmaceutics to maintain my hard-earned newfound lumps and bumps?

During the planning stages of a cycle – you should entertain ALL options for appropriate post cycle. In fact, PCT and supplementation is something that should be considered a part of the cycle. Waiting until the end to make these vital decisions is likely flirting with disaster.

Unfortunately, there are some necessary digressions or necessary evils to have a complete understanding of before continuing on our journey – that is, as I let you in on this fact in our last discussion – welcome to Endocrinology 101. Oh yeah, if you struggle with particular points of the science discussion that follows – it is imperative to consider yourself in a place that would make AAS use an inappropriate consideration in the first place.

Endocrine Debriefing

In chemical terms, steroids are naturally occurring lipids, or fat-soluble substances. They all have similar chemical structures and are ultimately derived from cholesterol. Steroid hormones, aside from the male sex hormones, include estrogen, aldosterone, progesterone, cortisol, and even vitamin D. Cholesterol is modified by special enzymes in a series of steps to become all of the various hormones.

Normally, over 95% of testosterone is secreted by the testicular Leydig cells. In addition to testosterone, the testes secrete small amounts of the potent androgen dihydrotestosterone and the weak androgens dehydroepiandrosterone (DHEA) and androstenedione. The Leydig cells also secrete small quantities of estradiol, estrone, pregnenolone, progesterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone.

Dihydrotestosterone and estradiol are derived not only by direct secretion from the testes but also by conversion in peripheral tissues of androgen and estrogen precursors secreted by both the testes and the adrenals. Thus, about 80% of the circulating concentrations of these two steroids is derived from such peripheral conversion.


Summary of Relative Contributions (appx. %) of major steroid origins

Testosterone
Testicular Secretion: ~ 95%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 4%

Dihydrotestosterone
Testicular Secretion: ~ 20%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 79%

Estradiol
Testicular Secretion: ~ 20%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 79%

Estrone
Testicular Secretion: ~ 2%
Adrenal Secretion: ~ 1%
Peripheral Conversion of Precursors: ~ 97%

DHEA-S
Testicular Secretion: ~ 10%
Adrenal Secretion: ~ 90%
Peripheral Conversion of Precursors: Not usually detected


In the blood, androgens and estrogens exist in either a free (unbound) state or bound to serum proteins. Although about 38% of testosterone is bound to albumin, the major binding protein is sex hormone-binding globulin (SHBG), which binds 60-80% of the testosterone (depending upon which source you get the figures from). This glycosylated dimeric protein is homologous to, yet distinct from, the androgen-binding protein secreted by the Sertoli cells. SHBG is synthesized in the liver, with the gene located on the short arm of chromosome 17. The serum concentrations of this protein are increased by estrogen, tamoxifen (discussed further in 2 parts), phenytoin, or thyroid hormone administration and by hyperthyroidism and cirrhosis and are decreased by exogenous androgens, glucocorticoids, or growth hormone and by hypothyroidism, acromegaly, and obesity. About 2% of the circulating testosterone is not bound to serum proteins and is able to enter cells and exert its metabolic effects. In addition, some of the protein-bound testosterone may dissociate from the protein and enter target tissues; thus the amount of bioavailable testosterone may be greater than just the amount of non-protein bound testosterone.


CONTROL OF TESTICULAR FUNCTION

I split this into the following two categories: Hypothalamic-Pituitary- <Leydig Cell / Seminiferous Tubule> Axis. From this point on, I will use the abbreviations HPLCA or HPSTA interchangeably with HPTA (more of a blanket term) – HOWEVER, we will get a BIT MORE SCIENTIFIC, because they are NOT the same and this mutual exclusivity certainly will pan out along this series!

Hypothalamic-Pituitary-Leydig Cell Axis (HPLCA)

The hypothalamus synthesizes a decapeptide, gonadotropin-releasing hormone (GnRH), and secretes it in PULSES every 90-120 minutes into the hypothalamo-hyphysial portal blood. After reaching the anterior pituitary, GnRH binds to the gonadotrophs and stimulates the release of both leutinizing hormone (LH) and, to a lesser extent, follicle-stimulating hormone (FSH) into the general circulation. LH is taken up by Leydig cells, where it binds to specific membrane receptors. The LH receptor is a G protein-coupled receptor containing seven transmembrane domains with a serine and threonine-rich cytoplasmic region containing a phosphorylation site and a 350- to 400-amino acid extracellular hormone-binding domain. The binding of LH to the receptor leads to activation of adenylyl cyclase and generation of cAMP and other messengers that ultimately result in the secretion of androgens. In turn the elevation of androgens INHIBITS the secretion of LH from the anterior PITUITARY through a direct action on the pituitary and an INHIBITORY effect on the HYPOTHALAMUS. Both the pituitary and hypothalamus have androgen receptors (more later). Experimentally, pure androgens such as DHT reduce LH pulse frequency, while estradiol reduces LH pulse amplitude. However, the major inhibitory effect of androgen on the hypothalamus appears to be mediated principally by estradiol, which may be derived locally through the aromatization of testosterone. Leydig cells also secrete small quantities of oxytocin, renin, corticotropin-releasing factor, inslin-like growth factor I (IGF-1), transforming growth factors alpha and beta, IL-1, lipotropin, beta-endorphin, dynorphin, angiotensin, inhibin, gastrin-releasing peptide, stem cell factor, substance P, and prostaglandins, which may be important for paracrine regulation of testicular function. These may be optimal future adjunctive targets.

Hypothalamic-Pituitary-Seminiferous Tubule (HPSTA)

After stimulation by GnRH, the gonadotrophs secrete FSH into the systemic circulation. This glycoprotein hormone binds to specific receptors in Sertoli cells and stimulates the production of androgen-binding protein. FSH is necessary for the initiation of spermatogenesis. However, full maturation of the spermatozoa appears to require not only an FSH effect but also testosterone. Indeed, the major action of FSH producing androgen-binding protein can be viewed as PURELY EVIL. I beg you not to look at it this way as it aids us to maintain high intratubular concentrations of testosterone (likely more an evolutionary effect for production of offspring in the realm of spermatogenesis, but the test concentration also has other advantages – we will discuss this in more detail later).

In addition to androgen-binding protein, the Sertoli cell secretes several other substances like LH does: GnRH-like peptide, IGF-1, transferrin, plasminogen activator (improtant side effect potential for steroid users), ceruloplasmin, mullerian duct inhibitory factor, H-Y antigen, and inhibin A and inhibin B. While I would love to talk about each of these factors as I find them fascinating future research items.

...

Originally Posted by dinoiii

PHARMACOLOGY OF AAS

AAS are a class of chemically related steroid hormones that promote both protein anabolism and masculinization. Chemically, they are analogues of testosterone. Pharmacologically, their dominant effect is net synthesis of protein in virtually all tissues that are capable of growth, including male reproductive tissue. Even effects that are commonly referred to as androgenic, for example, regulation of male sexual organs, can be considered to be anabolic; in fact, an androgenic effect has been described as an anabolic effect on sex organs (16).

Testosterone, other endogenous steroids, and hundreds of synthetic steroids fulfill this definition. The terms androgen and anabolic are OVERLY SIMPLISTIC and INADEQUATE, however, because some effects are not easily classified as anabolic or androgenic, and some are clearly neither (i.e. – decrease in SHBG). In fact, a remarkable feature of the AAS is their diverse and large number of effects. Virtually all tissues are affected in some manner, and often it is difficult to distinguish between primary and secondary effects. Further, individuals given the same dose sow a remarkable variability in response.

Despite intense research efforts (regardless of what many “authorities” suggest), NO steroid has been described that is purely anabolic OR androgenic. Furthermore, in healthy men, there is NO direct evidence for more than one receptor. Thus, the dual ability to promote growth and masculinize is inherent in the same molecule, therefore, the most appropriate designation remains anabolic androgenic steroid. Nevertheless, the term AAS is commonly shortened to “anabolic steroid” or “androgenic steroid” depending on the context. “Androgenic” is used for discussions that emphasize sexual differentiation, pubertal changes, virilization, and effects on primary and secondary organs of reproduction.


ANROGEN RECEPTOR

The notion of one receptor mediating androgenic effects in male reproductive tissue and another mediating anabolic effects in muscle tissue arose from the observation in experimental animals that some compounds exert anabolic activity and relatively little androgenic activity (17).

The hope of discovering an AAS devoid of androgenic activity fueled a concerted effort to synthesize and test new agents. Since nitrogen balance studies were cumbersome, a simple bioassay was developed that compared, in the same animal, the AAS-induced increases in weight of the prostate and of the levator ani muscle. The anabolic-androgenic ratio was interpreted as an index of relative dissociation of anabolic from androgenic activity. Although this assay did correlate reasonably well with nitrogen retention studies, the validity of the assay was later questioned. In addition, research on specific intracellular enzymes, differences in the affinity of compounds for receptor binding proteins, and differences in levels of receptors in various tissues showed that the diversity of responses could be explained by other mechanisms. Moreover, recent studies provide substantial evidence for only one receptor.

The androgen receptor has been isolated and characterized (18), and a cDNA that encodes the AR has been cloned and expressed numerous times during the ten years of research that brought us its characterization. Defects or single amino acid substitutions in the AR are associated with several diseases. Only one AR type has been discovered by either molecular biologic techniques or receptor-binding studies. The binding characteristics of receptors-isolated from reproductive tissue and from skeletal muscle are IDENTICAL (19). Antiandrogens also bind to the AR and compete with T and DHT for the binding sites. Perhaps the most convincing evidence for the one-receptor theory is research describing the clinical consequences of androgen receptor disorders and associated molecular biology of the androgen receptor gene (20).

Most of the effects of AASs are presumed to be mediated, like those of T in tissues that contain AR, which include reproductive organs, brain, kidney, liver, skin, skeletal muscle, cardiac muscle, bone, larynx, thymus, and hematopoietic and lipid tissue. You knew I would get to why all of this science stuff is important, especially considering PCT or even peri-cycle. Does anyone see the potential for side effects with the AR being expressed in all those endogenous tissues?

At the subcellular level, the effects are determined by the affinity, binding constant with the AR and molecular details of receptor DNA interaction, transcription, and translation. Within the target cell, the effects of AAS are presumed to be influenced by the same mechanisms that control the fate and effects of T. These include enzymes that activate and deactivate T, enzymes that control the activity of receptor androgen interactions, and differences in receptor content.


ABSORPTION, DISTRIBUTION, AND METABOLISM

None of the synthetic nonendogenous AASs have been studied as intensively as T. The synthetic agents are absorbed from the gastrointestinal tract, mucus membranes, skin, and intramuscular deposits. We have already discussed how most T circulates in the blood stream. It is important to note that the synthetic agents also have an affinity for SHBG.

The concentration of AASs and metabolites can be measured in serum and urine, and there are some data on concentration in serum relative to therapeutic effects; however, plasma levels are not commonly used to monitor dosing.

Free T diffuses into the cell where it may bind directly to the AR, undergo reduction of the C4-C5 double bond to 5-alpha-DHT by 5-alpha reductase, or be metabolized further. Both T and DHT bind to the same AR, although DHT is more tightly bound, leading to the hypothesis that we have all accepted as truth – DHT is the most active and potent intracellular androgen. Binding to the AR activates the complex, enabling it to interact specifically with DNA and activate specific genes. Some T is metabolized by aromatase to estradiol (actually still a bit more complex – see later), which binds to the estrogen receptor (ER). These important features of T metabolism emphasize that administration of T will result in a mixture of effects mediated by the T + AR and/or DHT + AR and estradiol + ER. In some cases, the effects at one receptor may be neutralized or enhanced by effects at the other.

The extent to which the effects of AASs are mediated at both ER and AR is less certain, in part because the metabolism of AASs has not been studied as extensively as that of T. Any synthetic AAS with a delta-4, 3-keto function is subject to metabolism by aromatase to the corresponding estrogens. A few estrogen metabolites of AASs have been described in humans, and in vitro studies indicate that many more are likely. Examples of AASs that are NOT substrates for aromatase are DHT, fluoxymesterone, mesterolone, and oxandrolone.

Receptor-binding studies confirm that ARs derived from muscle tissue or prostate tissue are the same, and that synthetic agents, T, and DHT bind to the same AR. All synthetic AASs undergo extensive metabolism primarily to hydroxylated and 5-alpha- and 5-beta-reduced metabolites. Most of these are excreted in the urine as sulfates or glucuronides. Various metabolites of synthetic AAS have been found in subcellular fractions of target tissues and their binding to AR has been characterized. Unlike T, however, 5-alpha-reduced metabolites of 17-alpha-methyl AASs are NOT more active than the parent compound (which likely dictates perceived differences in effectiveness between things classically considered AAS and those in the former/current PH/PS class).

Now, rationale guiding the basis for use of AAS by athletes likely centers on the fact that skeletal muscle tissue differs from other androgen-responsive tissues in that 5-alpha-reductase activity is low and T is present in greater amounts than DHT. Thus, T is the dominant intracellular agonist in muscle. In the experimental animal, the concentration of ARs varies markedly from one muscle group to another, and those with the higher concentrations respond the most to androgen (these effects are like adipocyte-alpha/beta receptor concentrations and what entirely OFFERS a complete model to understanding body composition – remarkably, many remain baffled – oh yeah, the authorities forget to tell you that you are STILL A SUBJECT OF YOUR GENETICS and without employment of REAL LIFE “TRICKS” with your usage, you are STILL GOING NOWHERE!!!). This parallels the observation that, in human males, the predominant response seen to anabolics remains that the back, chest, and upper arm are going to respond better than other muscle groups to AAS. HAS ANYONE THAT HAS USED ANABOLICS OF ANY VARIETY NOT EXPERIENCED THE BEST BODY COMPOSITION CHANGES IN THESE AREAS? I didn’t think so.


GLUCOCORTICOID RECEPTORS

Now, our discussion doesn’t end with the AR. One alternative hypothesis that does NOT require ARs is that AASs promote positive nitrogen balance and muscle growth by acting as an antagonist at glucocorticoid receptors (GRs), thereby inhibiting catabolic actions of glucocorticoids (20). This hypothesis is supported by studies in adrenalectomized-castrated animals (21) and by cell culture experiments showing that, in cells that express AR and GRs, oxandrolone suppresses glucocorticoid action via a novel type of cross-talk between the receptors (22).

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Originally Posted by dinoiii

ONSET, DURATION, AND REVERSIBILITY OF
ADVERSE EFFECTS

The onset of hormone suppression may be very rapid. Methyltestosterone, 25 mg/day for 3 days followed by 240 mg/day for 3 more days led to highly significant declines in serum T, DHT, FSH, and LH. Three days after the 6 days of methyltestosterone, the levels of T and DHT were still low, while FSH and LH had returned to normal.

The hallmarks of reversibility are marked variability and unpredictability. Some effects in some individuals rapidly reverse and others very slowly IF AT ALL. At one extreme, diminished height resulting from premature closure of epiphyseal plates is completely irreversible, while elevated levels of ALT and AST rapidly reverse. Of course, I have pointed out that the premature closure of epiphyseal plates in my best efforts of thought would be attributed to increased estrogenic turnover via aromatase accounting for this discrepency when AAS are inappropriately come off of perhaps citing an even more imperative rationale for proper PCT.

Cholestatic jaundice and peliosis hepatis (both talked about at length later in this article) ARE usually reversible and to some extent, hepatic adenoma will regress with the discontinuation of AASs. Voice changes are particularly slow to change.

Most of the virilizing effects in females are considered irreversible, although detailed studies are NOT available. Changes in body composition take many months to subside fully provided inappropriate PCT – I am not a firm believer in the notion that NONE of the gains achieved on a cycle can be retained. After a 12-week course of T enanthate, body fat and LBM did NOT return to baseline for approximately 6 months and, after 1 year of ND, the forearm fat content remained low for AT LEAST another 6 months.

Hypogonadotrophic hypogonadism induced by AASs is reversible, although the rate of recovery may be quite slow and depends in part on the particular AAS that was used and the duration of use. For example, following a 2-week course of methandienone (30 mg/day), FSH and LH returned to baseline in 7 days, but T levels were still low after 2 weeks, whereas, after 12 weeks of fluoxymesterone (10-30 mg/day), plasma levels of T were back to normal in 1 to 2 weeks. The esters of nandralone and T produce the longest lasting effects. In contraception studies with T esters lasting several months, the sperm count may not return to normal for 20 to 30 weeks after drug discontinuation. Athletes taking high doses of N esters frequently experience azospermia, which may last for 20 weeks after drug discontinuation, and plasma levels of FSH, LH, HDL, cholesterol, and T take 20 to 50 weeks to recover. Occasionally, azospermia may still be present after 1 year without steroids. We will explore the topic of azospermia more in the pharmaceutic subset of this series.

Studies do but a couple things; they tell us that the degree of the hypogonadism is highly variable, and the severity may be extreme. The time to total recovery is correlated with some combination of the total dose, duration of treatment, and serum half-life of the agent. The ways in which this process of recovery may be expedited will be discussed in the remaining sections of this series. PLEASE DO NOT CONSIDER FULL EMPLOYEMENT OF THESE STRATEGIES UNTIL ALL REMAINING PARTS HAVE BEEN RELEASED AND OF COURSE, ONLY WITH THE GUIDANCE OF YOUR OWN EXAMINING PHYSICIAN OR THE INDIVIDUAL(S) ASSUMING THAT ROLE.
PHARMACOLOGY OF AAS

AAS are a class of chemically related steroid hormones that promote both protein anabolism and masculinization. Chemically, they are analogues of testosterone. Pharmacologically, their dominant effect is net synthesis of protein in virtually all tissues that are capable of growth, including male reproductive tissue. Even effects that are commonly referred to as androgenic, for example, regulation of male sexual organs, can be considered to be anabolic; in fact, an androgenic effect has been described as an anabolic effect on sex organs (16).

Testosterone, other endogenous steroids, and hundreds of synthetic steroids fulfill this definition. The terms androgen and anabolic are OVERLY SIMPLISTIC and INADEQUATE, however, because some effects are not easily classified as anabolic or androgenic, and some are clearly neither (i.e. – decrease in SHBG). In fact, a remarkable feature of the AAS is their diverse and large number of effects. Virtually all tissues are affected in some manner, and often it is difficult to distinguish between primary and secondary effects. Further, individuals given the same dose sow a remarkable variability in response.

Despite intense research efforts (regardless of what many “authorities” suggest), NO steroid has been described that is purely anabolic OR androgenic. Furthermore, in healthy men, there is NO direct evidence for more than one receptor. Thus, the dual ability to promote growth and masculinize is inherent in the same molecule, therefore, the most appropriate designation remains anabolic androgenic steroid. Nevertheless, the term AAS is commonly shortened to “anabolic steroid” or “androgenic steroid” depending on the context. “Androgenic” is used for discussions that emphasize sexual differentiation, pubertal changes, virilization, and effects on primary and secondary organs of reproduction.

.

Originally Posted by dinoiii

ANTI-ESTROGENICS

(1) Aromatase Inhibitors

The aromatase enzyme is the rate-limiting step in the conversion of androgens to estrogens. Aromatase is an enzyme complex containing a cytochrome P-450 hemoprotein and a flavoprotein, nicotinamide-adenine dinucleotide phosphate P-450 reductase. The cytochrome P-450 catalyzes a series of 3 hydroxylations of the androgen substrates androstenedione and testosterone. Because the aromatase cytochrome P-450 has little homology to other P-450 enzymes, it has been assigned to a separate gene family designated CYP19.

The aromatase enzyme selectively catalyzes only the production of estrogens, whereas other similar enzymes govern the production of other steroid hormones, including glucocorticoids, androgens, and mineralocorticoids. The optimal way to decrease estrogen production is to selectively target the aromatase enzyme without inhibiting the activity of the other enzyme systems.

Aromatase production sites in males include: adipose tissue, liver, muscle, placenta, and hair follicles. One problem with aromatase inhibition is that it is incomplete because increased estradiol synthesis signals the pituitary to correct this hormonal discrepency, increasing both FSH and LH secretion. FSH is a more direct stimulant of extra aromatase whereas LH stimulates androgenic substrate for the conversion. You are actually COMPOUNDING THE PROBLEM if you are not careful.

Aromatase inhibitors are of two general types: type I, referred to as suicide inhibitors (I am particularly adverse to this dubbing!), and type II equal competitive inhibitors.

Once a suicide inhibitor binds the aromatase enzyme, the sequence of hydroxylations is initiated, but the hydroxylations produce a covalent bond between the enzyme and the inhibitor that irreversibly blocks the activity of the enzyme. After exposure to a suicide inhibitor, aromatase enzyme can only be restored with new enzyme synthesis.

Competitive inhibitors reversibly bind to the active enzyme site, and either no enzyme activity is triggered or it has no effect. The inhibitor can dissociate from the binding site to allow renewed competition between the inhibitor and the substrate for binding to the active binding site. For the effect of a competitive inhibitor to persist, a constant concentration of the inhibitor IN EXCESS OF THE SUBSTRATE MUST BE PRESENT.

ZEE CURRENT CROP:
4-androstene- 3, 6, 17-trione / androst-4- ene-3,6,17-trione
1, 4-androstadiene - 3, 6, 17-dione
6, 17-keto-etiocholeve-3-ol tetrahydropyranol
3, 17-ketoetiochol-triene
3’, 5, 7-trihydroxy-4’-methoxyflavone
6-acetoxy-3-hydroxy-17-keto-etioallocholane
17a-methyl-17b-hydroxyl-3-keto-delta 1,4,6-etioallocholtriene
4-hydroxyandrostenedione

I wrestled up the various brands containing the ingredients listed above that fall under the umbrella of “anti-estrogenics,” in many cases, aromatase inhibitors. These compounds will be addressed throughout this series because they are the most often hyped and subsequently the most often sought after if a supplement is to be on board in the post cycle realm, sometimes at the expense (mistakenly so) of the basic latter supplements I endorse to follow.

(2) Estrogenic Channeling Agents

Indole-3-Carbinol

Only one kind of vegetable interferes with the estrogen pathway and that is a cruciferous vegetable. These get there name from the crosslike stem they all have in common, from broccoli to cauliflower. European women who ate more cabbage had lower breast cancer death rate. Cruciferous vegetables decreased the risk by 40 percent in a Wisconsin study. So, how do they work and why would I include this talk of female breast cancer in a study who’s primary target remains males in the post-cycle time frame?

The secret ingredient is called indole-3-carbinol, which channels the breakdown products of estrogen into far more “good” estrogen (2-hydroxyestrone) than “bad” estrogen (16-alpha-hydroxyestrone). As with good and bad cholesterol, you can increase or decrease either amount of estrogen. Indole-3-carbinol can double the amount of good estrogen while decreasing the bad, which the Journal of the National Cancer Institute reported to decrease the amount of “bad” estrogen thereby subsequently leading to a decrease in breast cancer in Finnish women studied.

The rationale for it being discussed here is one of pure origin, however, similar application can be applied to males in the post-cycle time frame. That is, a decrease in the “bad” cholesterol remains of utmost importance in both scenarios, while the potential consequence of its existence does not share any similarity.

While 1% of breast cancer is found in males, it is NOT breast cancer prevention that is found to be the largest benefit here. The shunting described above that suggests the favoring of 2-hydroxylation over 16-alpha-hydroxylation may reduce risk of clinically evident prostate cancer (12). This shunting has another effect: it aids the liver’s Phase I and Phase II enzymes allowing a bit more wear and tear from the cycle (especially encouraging news for the C17-alkylated oral users). Oh yeah, gentlemen there is this shunting effect that would also be beneficial in fat deposition or feminizing effects seen in the post cycle time frame.

We’ll explore some UNIQUE dosing parameters as well as absorption protocols for the most benefits of this extract.

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Originally Posted by dinoiii

PRO-TESTOSTERONE

DHEA (dehydroepiandrosterone)

DHEA is a natural steroid hormone produced from cholesterol by the adrenal glands. Some bodybuilders use it for PCT because it is purported to get the libido back, and some studies suggest that it is effective in regenerating atrophied testicles. It is also said to give you a better sense of well being, restore natural test production, and is not suppressive. DHEA is subject to being aromatized in peripheral tissues to estradiol. This could be exponentially increased during the post cycle period.

When evaluating what may be appropriate for the post cycle period, the interjection of items at this point in the steroidogenesis pathway are done at an inopportune time. DHEA has the dual negative potential to first increase estrogens (there is nothing to say pathways will shunt as you desire them to) and second, to decrease HDL and this could not be a more inopportune time for this level to be even hypothetically affected by continued exogenous substances. Further discussion of this aspect will be seen through this series’ unfolding as well as below.

Cordyceps (Cordyceps sineus)

A handful of studies conducted in Chinese subjects have shown increases in libido and restoration of testosterone and DHEA levels (from low to normal) following cordyceps supplementation. In addition, using cordyceps as a way to normalize these suppressed DHEA levels can help modulate the cortisol : DHEA ratio within a lower (and healthier) range. Because more than 200 different species of the cordyceps mushroom exist, it is important to look for the one on which the majority of the research has been conducted: the Cs-4 strain (typically standardized for mannitol content as a marker compound).

Tribulus Terrestris

Here is an example of a supplement with quite the storied past. Tribulus terrestris has a long history of use in Eastern Europe and China as a liver tonic and natural hormone stimulator. It has also been used for sexual dysfunction and infertility. Western practitioners became aware of the Bulgarian pharmaceutical (Sopharma) product designated to treat hormonal insufficiency and a potential fertility therapy.

Tribestan is the trade name of a formula with tribulus and other herbs sold in Eastern Europe. After a strong underground following among bodybuilders brought it to the U.S., Sopharma licensed the formula to several American supplement companies for sale here. Company claims purport up to 30 percent testosterone increases in men and subsequent increased men’s libido, strength of erections, and sperm production. Though the purported studies that support these claims are still outstanding in presentation, the supplement’s cult following certainly raises an eyebrow.

The mechanism of action is purported to be increased secretion of LH from the pituitary. One thing warranting exploration is how tribulus does have a female-SPECIFIC stimulatation of FSH production. Again, this does not appear to be the case in males.

I have discussed at length in my Tribulus article some of the potential overlooked benefits, but I am going to step outside of that series here and report a link I see to another hormonal system that plays an important role in the post-cycle period. Tribulus terrestris provides a safe, non-hormonal stimulation of the endocrine system emphasizing testosterone AND estradiol (again, it is an LH stimulator) production and liver enhancement. The important point I want to make is that both of the aforementioned effects contribute to and augment the metabolic action of HGH and IGF-1 as both testosterone and estrogen increase their production.

Additionally, imperative effects of tribulus during the PCT time frame could be the improved libido production and increased sperm count noted. It also acts as a liver tonic that further contributes to better hormone production and phenomenal potential after C17-alkylated hormonal use. A little biochemistry recall: the liver synthesizes hormones from cholesterol and breaks down fats to EFAs, which also play major roles in hormone production.

One more positive. Tribulus boosts the break down of proteins to amino acids for the creation of new muscle cells, which directly impacts growth hormone. The more muscle you have, the more endogenous HGH the body will produce – and vice versa. The effect tribulus has on protein greatly complements the actions of growth hormone and creates better energy usage, exercise recovery, and stamina. For this reason, the herb offers significant benefits for professional athletes despite negative press.

From body composition studies that didn’t show instantaneous “results” – the herb found itself placed very far down the list of some bodybuilder’s arsenals. This is unfortunate because bodybuilding is a complete science (ok, so it may be my dream that all consider bodybuilding that, BUT THE HUMAN BODY VERY MUCH IS THE SCIENCE!!!)

It does not end there, the fruit and root of Tribulus terrestris also contain metabolites like phytosteroids, flavanoids, alkaloids, and glycosides. These bioactive compounds have a strong and beneficial effect on the immune, sexual, and reproductive systems. It also reduces cholesterol, helps to prevent kidney stones and has been reported to offer a sense of well being (more later on psychiatric effects of cycle and post-cycle use). One clinical study revealed it has the ability to dilate coronary arteries, making it an ideal heart tonic (STAY TUNED TO THIS ARTICLE FOR MORE HERE!)

Chaste Berry (Vitex Agnus – Castus)

For menstrual cycle irregularities and PMS – yes.
For testosterone ... Ummmmm – N-E-X-T!

MEGA Minerals (Zinc/Magnesium)

Oftentimes, our being caught up in the marketing hype of “ZMA” formulas to increase testosterone levels is what misleads the consumer to thinking these minerals have no application. This could NOT be a bigger misconception, especially during the post-cycle time frame. We will address zinc and magnesium one by one.

Magnesium Glycinate (Patent #4,830,716)
According to recent Hanes and Gallop surveys, at least 72% of all adult Americans fall short of the U.S. RDA for magnesium (bodybuilders whose nutrient tallies increase precipitously are the worst offenders). Serum (blood) magnesium levels are NOT an accurate test for total body stores of this mineral because magnesium is primarily a cellular mineral. Also, stress depletes this mineral rapidly. During the post-cycle time frame, the body experiences a significant stress load with its newfound exogenous extraction and anabolic depletion. Thus, supplementing magnesium is of DIRE concern for individuals going through PCT.

Magnesium is a catalyst for at least 30 organic functions. Some of its benefits include: protein synthesis, regulation of parathyroid hormone release which regulates bone calcification, cellular respiration, nerve transmission, prostaglandin synthesis, and cardiac muscle health.

Some of the most alarming magnesium deficiency symptoms which are rarely diagnosed by the medical profession relate to the following disorders: hypotension, hypertension, kidney stones, muscular weakness, neuromuscular irritability, hemolytic anemia, bronchial asthma, organic brain syndrome, migraine headaches, tachycardia, cardiac arrhythmia, myocardial infarction, edema, hyperkinetic behavior, insomnia, severe muscle pain, seizures, vertigo, chronic fatigue syndrome, diabetes, coarse muscle tremors, osteoporosis, psychiatric disorders, shortness of breath, and poor pulmonary function.

Those that like the “you can get enough magnesium from diet alone” proponents are very far off! This is in addition to most supplemental magnesium coming in oxide, aspartate, sulfate, or hydrochloride forms which can cause diarrhea and abdominal cramps among sensitive individuals. This is further compounded by combining magnesium with other minerals – NAMELY calcium WHICH IMPEDES the absorption of magnesium in these forms, yet most formulas boast combos of these two vital minerals in some way, shape, or form. Magnesium glycinate, on the other hand, is a patented (U.S. Patent #4,830,716) revolutionary process of chelating magnesium to glycine so that magnesium is absorbed like an amino acid. It is so well absorbed that it is NOT dependent on stomach acid or diet. It is released easily into the target organs for higher absorption and nutrient density.

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Zinc
An essential nutrient and a catalyst for over 30 bodily functions. Zinc deficiency plays a major role in the following health conditions: acne, anorexia nervosa, delayed sexual response, growth impairment, hair loss, fatigue, memory loss, macular degeneration, high LDL cholesterol, poor appetite control, impaired night vision, impotence, infertility, acuity of taste and smell, poor protein synthesis, increased susceptibility to infection, skin lesions, propensity for diabetes, prostate enlargement (see below), recurrent colds and flu, and slow wound healing. Major food sources for zinc are fish, shellfish (be careful here, however as shellfish remain a major source of iodine as well and this can be a real concern for acne sufferers – especially in PCT time frame – this is the one food association that has been supported by research), meat, eggs, soy (though I don’t encourage the use of this in PCT), nuts/seeds – especially sunflower seeds.

HERE’S THE KICKER! With copious caloric intake during a cycle, it is VERY easy to become downloaded with excess dietary sugar which DEPLETES ZINC STORES QUICKLY – it is imperative to cut this depletion off at the pass and make certain supplemental zinc is taken throughout the cycle to make the transition to PCT much easier. Also, compounds in insoluble fibers, particularly whole wheat and psyllium (a bodybuilder’s favorite supplemental source of fiber), BLOCK zinc’s absorption.

Zinc is found in many forms when added to dietary supplements (oxide, aspartate, picolinate, sulphate, chelate, gluconate). Zinc in pill form tends to be absorbed best with the least side effects if in glycinate/arginate, amino acid, or gluconate bound forms. This is not to be confused with the orthomolecular dosing patterns sometimes suggested for immune ailments – for them, mouth absorption (either gargling with liquid zinc sulfate or sucking zinc lozenges) is essential.

We will address dosing parameters for the PCT time frame in the next part of this series

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Originally Posted by dinoiii

ANTIOXIDANTS

It is not possible to avoid exposure to all the carcinogens and chemicals in the environment. We must still live in this world. Hesitating with fear of “what might be out there” will only rob us of a full and abundant life. The mere fact that we need oxygen to live puts us at significant risk for oxidative stress. There is not more significant a potential oxidating time-frame than during a anabolic cycle as well as the subsequent post-cycle period that follows.

It seems logical that if this oxidative stress is indeed the cause of various detrimental pathological processes, including cancer, antioxidants used to bring free radicals back into balance would lower the potential risk of such processes. This logic proves true.

Studies show that supplementation of a good diet over a twenty-week period of time with vitamins C, E, and beta-carotene resulted in a significant decrease of the oxidative damage to DNA with the use of various exogenous substances (1). Vitamin E has also been shown to protect against exercise-induced damage (2).

Alpha Lipoic Acid (ALA, lipoic acid, thioctic acid)

ALA was discovered in the 1930s and subsequently isolated during the 1950s. Chemically, it sounded very sexy to us science dorks as octanoic acid – to which it is very similar. ALA is actually comprised of a 6,8-dithiolane octanoic acid and a 1,2 dithiolane-3-valeric acid or a 1,2 dithiolane-3-pentanoic acid, BUT all that science jargon is NOT very marketable when the name virtually stretches completely around a dietary supplement bottle.

Originally classified as a vitamin, it was later categorized as an essential coenzyme in 1951 when scientists discovered that is was intrinsically involved in the energy processes of cell mitochondria. Within a few years, German physicians began prescribing it for the treatment of Amanita mushroom poisoning and nerve disorders. It was not until 1988 that scientists learned of its powerful antioxidant action. In addition, the fact that this antioxidant was both fat and water soluble made it more impressive – able to confer protection from free radicals both inside and outside the cell.

On a pharmacologic level, ALA is a disulfhydryl coenzyme that converts to dihydrolipoic acid once inside cellular structures. Dihydrolipoic acid is considered even more powerful free radical deactivator than the original acid. While ALA appears to have the ability to deactivate both hydroxyl and single-oxygen free radicals, its dihydrolipoic form has the additional attribute in neutralizing peroxyl and peoxynitrite free radicals. This latter type of oxidation is considered particularly damaging in that it contains both oxygen and nitrogen-based free radicals.

Free radicals tend to have two sources while on cycle. The first is through byproduct of exogenous anabolic agent metabolism (increasingly so with 17 alpha-methylated variant PH/PS’s). The second, unbeknownst to many gym rats, happens to be what we in fact hold so dear – exercise itself which during cycle tends to increase surreptitiously.

Cellular glutathione (discussed later in relation to the liver’s metabolic elimination of various toxins) is produced by the body and, like other antioxidants, works to neutralize free radicals. Trying to artificially boost glutathione levels has been difficult, and while oral glutathione supplements are available, they must go through the gastrointestinal route before entering the blood stream. Unfortunately, little, if any, glutathione actually survives the digestive process. Consequently cellular levels are not significantly increased by oral supplementation.

All this glutathione talk in conjunction with exercise, as beneficial as it is, pose great oxidizing potential to your body. Exercising on a regular basis can initiate the release of free radicals within our cellular systems. This cannot be understated with aerobic activity, but during cycle nine out of ten times, the concern is with anaerobic counters. Alpha-Lipoic Acid, its potassium salt, and the dihydro metabolite will all be considered as this series progresses.

Carnitine

Whether non-altered amino, acetylated, or propionyl versions – the thought process surrounding its use is that this compound is responsible for transporting fats into the mitochondria where they then can be converted to energy. While the research has NOT panned out in this respect (i.e. – showing statistically significant body composition changes secondary to fat loss), L-carnitine’s counterparts (namely the acetylated) has turned up very interesting results in the research of brain-deteriorating disorders [literally 100’s of studies]. You need it to be in the acetylated form to allow it the opportunity to pass through the blood brain barrier. In fact, recent studies have identified this compound as one of the most significant anti-aging compounds for the brain and nervous system. It has been shown to actually prevent neuron death due to its release and synthesis of choline.

While the above is a good plan for general brain health, a more beneficial rationale for the use of one of the aforementioned variants is through indirect rationale to be used as an anticatabolic. Why? Because when the neurotransmitters in the striatal cortex (acetylcholine + dopamine here) are working well, they help keep cortisol under control. Cortisol, during the stressful transition into post-cycle is highly catabolic to muscle.

It is also a great PCT addition due to its potential antioxidant properties (anti-lipid peroxidation is actually more appropriate here), which is the proposed hypothesis behind its dramatic reductions of cardiac arrhythmias, cardiomyopathy, muscle weakness, elevated triglycerides, mitral valve prolapse, and atherosclerosis. The general thought process that dictates the mechanism of action here is one of an antioxidant nature. While many may be thinking – big deal. In the post-cycle time frame, continue to read the information that follows paying particular attention to the dyslipidemia / hypercholesterolemia sections below.

Well, how about the claims of increased testosterone? The source of this claim is from ONE study in rats – and btw, the study did NOT show increasing testosterone through ALC use, but a prevention of decreased testosterone in times the rats were “stressed.” Ever seen a stressed rat?

One additional note is that many companies suggest ingestion of ALC as one approaches bedtime. This is AN ABSOLUTELY TERRIBLE IDEA! Again, metabolic trickery will earn you a good PCT and metabolic trickery ONLY. The hormonal balance trade in here would be acetylcholine + dopamine to dominate a period when serotonin should be highest. We’ll discuss some great strategies here in the next part of this series.

Additional positives to use of this supplement in the PCT time frame can be imagined with the hypotheticals I have supplied in the supplement section of my BodyOpus: Reloaded article.

ACES

The research literature regarding ACES (Vitamins A, C, E, and the mineral Selenium) definitively supports their important role in the protection against “free radical formation,” cancer, and heart disease. They all help strengthen the immune system and are powerful anti-aging nutrients – two things of utmost importance following a cycle.

I don’t think the question is whether to include ACES in a supplemental formula BUT how to optimize their bioavailability with no side effects. Water dispersion for the fat-soluble vitamin supplements A and E is helpful so that they will be absorbed even if no fat is available. Dry vitamins A and E are beneficial for preventing excess skin oiliness (something significant with long-term heavy androgen use in some individuals). Recent research has shown that adding a small amount of mixed tocopherol (instead of alpha only) from an oil source enhances the health benefits of Vitamin E. Too much Vitamin E can actually weaken the immune system (NOT ideal during the post cycle time frame). Dosing protocols will become apparent later in this series.

Vitamin C is critical for human health. Because we are one of the only 2 animals who cannot manufacture it, we need to supplement this vitamin in our diet. If we had no outside source of Vitamin C, we would get scurvy, which was a common cause of death among the British navy several centuries ago. Excess acid can be caused by taking too much Vitamin C without buffering it with a small amount of calcium carbonate. For optimum bioavailability, it should be taken with bioflavonoids. Quercetin is an excellent, non-allergenic choice. I will make note here that the post-cycle time frame (despite all the misinformation about decreasing cortisol levels) is the ABSOLUTE WORST TIME to take significant quantities of Vitamin C for rationale that will unravel as this series unfolds.

Selenium is an essential mineral. In parts of the world where selenium is deficient, cancer is far more common. Recent research has suggested that with as little as 200 mcg supplemented daily, selenium offers tremendous protection against several types of cancer. However, too much selenium (over 400 mcg daily on a long term basis) can be very toxic.

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Originally Posted by dinoiii

HEPATOPROTECTANTS (Liver-Protectants)

Virtually all AASs alkylated at the C17 position are associated with modest elevations of alanine (ALT) and aspartate (AST) aminotransferases. Such elevations are extremely common, probably dose-dependent, rarely exceed twice the baseline level, and usually regress even if the AASs are continued. This enzymatic elevation is the result, however, of increased metabolic processing offering a newfound daily exposure to substances toxic to our bodies while on cycle. There has been ONE EXCEPTION that I must note in the literature of a bodybuilder who used T, stanozolol, and methylandrostenediol and developed transaminase levels exceeding 5000 IU/L. This imposes quite the load to carry for the liver coupled with the already incredible overload it faces on a daily basis. Therefore, it is logical to think that all of us can benefit by preventing liver damage and the subsequent development of disease if we embark on these type of regimes.

Although the aforementioned effects on AST and ALT are considered hepatic in origin and toxic, I have spoken at lengths in previous posts about the fact that other tissues can contribute as these values are NON-specific, AND many other serum markers of hepatotoxicity are NOT affected by AASs.

Infrequently, AASs cause cholestatic jaundice characterized by elevated bilirubin, stasis of small bile ducts, and reversal after cessation of AASs. Cholestatic jaundice is associated with all oral AASs and has not been convincingly linked to esters of T or N. In most reviews, the incidence is a few percent, although in one series 17% developed jaundice.

Knowing that in its earliest stages, malfunction of the liver RARELY causes ANY symptoms and that conventional medicine has very little to offer in treatment of liver disorders, it seems wise to remember that prevention is the best cure. We are fortunate today to have access to natural liver-protecting remedies that are safe, effective, and without significant side effects.

Before we address these agents, we must digress momentarily and address what happens on a more microscopic level. The smooth endoplasmic reticulum of the liver is the essential organelle involved in removing toxic substances from the human body. One way this organelle goes to work is through its ability to generate high concentrations of glutathione, a powerful antioxidant composed of the following three amino acids: cysteine, glutamic acid, and glycine. When glutathione encounters a toxin, such as metabolites of androgen breakdown, it immediately attaches to it, making the substance become more water-soluble. Once it is water-soluble state, the toxin can then be excreted safely via the urine, hopefully without causing any damage.

N-acetylcysteine

All the hoopla that has been generated for N-acetylcysteine (NAC) likely originates from the Acetaminophen (Tylenol, paracetarnol) overdose literature. Consuming 10 grams or more of Acetaminophen has the potential (individual tolerance will depend on volume of distribution) to cause significant toxic effects, perhaps even subsequent death if overwhelming the various enzymatic processing systems (supersaturation).

Accumulation of the liver metabolite N-acetyl-p-benzoquinone(imine), which is responsible for hepatotoxicity through reaction with sulfhydryl groups of hepatic proteins (enzymes) by forming covalent bonds and eventually saturates these enzymes for glucuronide and sulfate conjugation. This saturation makes an alternative glutathione conjugation pathway (cytochrome P-450 dependent) more important. If hepatic glutathione is depleted, the reactive metabolite accumulates and may cause hepatic damage by interaction with cellular macromolecules, such as DNA and RNA. Acetylcysteine provides sulfhydryl groups for hydrolysis to cysteine, and it protects the liver from reactive acetaminophen metabolites.

SAMe (S-adenosyl-methionine)

When the liver is so overwhelmed by toxins it cannot produce enough glutathione, part of the concentration burden falls to SAMe, which is a necessary component of glutathione’s creation. Not coincidentally, the concentration of SAMe in the liver is one of the highest in the body.

Based on published clinical trials, elevating SAMe levels can have a beneficial effect on many conditions. As a preventative agent, SAMe is so powerful that it can reverse the effects of chemicals and alcohol as they occur (5). Studies also show that low SAMe levels create a toxic environment that can increase liver cancer risk(6).

Research has shown that SAMe can prevent and, if discovered early enough, even reverse this condition. There was a rodent study published in Toxicology and Applied Pharmacology, SAMe completely prevented fatty liver when given at the same time as alcohol. Of course, the dosages need to be adjusted for volume of distribution variations (7). Additionally, it is a worthwhile mention that SAMe therapy has also gained success against the battle with cholestasis – a potential beginning to the more fatal cascade that is the broad spectrum of biliary disorders.

Silymarin

From the seed of the milk thistle plant, this herb has been used for centuries to treat liver cirrhosis, chronic hepatitis, “fatty” liver, and inflammation of the bile duct. More than 300 clinical and experimental studies have demonstrated its effectiveness.

Silymarin works by slowing the entrance of toxins into liver cells. It also prevents free radical damage AND stimulates the production of NEW liver cells. As individuals age, a healthy liver is crucial for detoxifying additives in foods, medications, and environmental pollutants. If the liver is not operating optimally, fatigue, headaches, and weight gain often ensue. Thus, silymarin is a very safe preventative that can be taken daily. The only side effects usually experienced have been looser stools for the first few days of use.

While I have posted protocols to its usage in the post-cycle realm in the past, I will readdress this issue in the next part of this series.

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Originally Posted by dinoiii

NEOPLASIA

Hepatocellular Adenoma and Carcinoma

AAS administration HAS been associated with a variety of histologic types of hepatic neoplasia, ranging from benign adenoma to histologically malignant adenocarcinoma. In doing a COMPLETE review of cancer registries and literature surveys, 91-androgen-associated tumors were discovered, of which 48 were discounted either because lack of convincing histology or because they occurred in people with Fanconi’s anemia, which itself is associated with neoplasia. Despite the histologic characteristics of hepatic carcinomas, their clinical behavior IS benign: they do not metastasize; they are not associated with elevated alpha-fetoprotein; and they usually BUT NOT ALWAYS regress with discontinuation of the AAS. The median time of androgen exposure before diagnosis is 5 years and the latency is 2-30 years. Four cases of hepatic angiosarcoma have been associated with AASs. AASs are NOT mutagenic in the Ames test.

Peliosis Hepatis

This unusual lesion is characterized by micro- and macroscopic blood-filled hepatic or splenic cysts. Because of deaths and serious morbidity due to spontaneous bleeding, this is the MOST SERIOUS COMPLICATION of AASs. The lesion regresses with discontinuation of the AASs. At least 70 cases have been reported, and many of them were being treated with oxymetholone or MT for anemia or hypogonadism. Peliosis hepatis has been reported with ALL commonly used oral AASs, and to a lesser extent with T and nandrolone esters. Autopsy series report a high incidence of unrecognized peliosis in patients treated with oral AASs.



[Author’s Note: The two aforementioned conditions are NOT associated with toxic metabolite. I mention them in a PCT article because of their usual regression with cessation of the exogenous anabolic substance and their potential implication. Continued monitoring for signs of regression are in patient’s best interest. The literature does NOT site supplement NOR pharmaceutic treatment modalities for either of these conditions.]

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PROSTATE HEALTH

The prostate gland; is it anything more than a potential troublemaker? It is often estimated that a number approaching 100% of ALL men will suffer from symptomatology secondary to prostate enlargement (especially with increasing age) at some point in their life. Until trouble strikes, however, the prevailing attitude holds that this obscure gland is probably best ignored.

The prostate was first described by an Italian physician, Niccolo Massa, in the renaissance – roughly 3,000 years after references to urological diseases that plagued ancient Egypt in 1550 BC. In 16th-century Europe, a French military surgeon named Ambroise Pare frequently took embalmed cadavers home to study and practice new medical techniques. Though his family might not have appreciated such unorthodox houseguests, medical science – and urology in particular – owe Pare a considerable debt. He was the first to recognize that the prostate gland was a distinct organ, separate from the bladder. He detailed the gland’s intimate relationship to the seminal vesicles and ejaculatory dusts and explained how it operates during ejaculation.

The prostate’s troublemaker potential is unique. No other secondary organ develops cancer or enlarges with aging. We don’t see benign or malignant overgrowth in the seminal vesicles, vas deferens, or Cowper’s glands, though these organs are exposed to many of the same environmental conditions, genetic factors, and hormonal influences as the prostate.

The post-cycle time frame mimics the aged male in a couple of hormonal regards. Testosterone production and secretion is impaired and estrogen:testosterone ratio is grossly exaggerated.

Saw Palmetto (Serenoa rapens)
incl. nettle root studies + zinc

Saw palmetto is a palm tree native to Florida. Saw palmetto’s benefits can be traced back to the early 1700s when aborigines of the Florida peninsula depended largely upon the berries. Saw palmetto berries were also used by American Indians to treat “atrophy of the testes, impotence, inflammation of the prostate, low libido in men, and as a general tonic to nourish the body (3).” Early American settlers also used the saw palmetto berry to treat problems associated with the genitals, urinary tract, and reproductive system. Ancient Mayans used the berries to treat disorders of the genitourinary tract (4).

While having had gained widespread support overseas and with our neighbors to the north for many years, the United States was a tad more reluctant to accept this herb gaining acceptance as the “plant catheter.” This alternative name was due to its therapeutic offerings on the neck of the bladder and the prostate gland (3).

A couple articles from about a decade ago help to reveal the mechanism of action of saw palmetto. Despite the time that has surpassed, the insight supplied by these two studies has been unsurpassed. The first article, published in the new journal Phytomedicine, explores the 5-alpha-reductase inhibiting properties of the free fatty acids in the saw palmetto berries (13). This activity is not only critical to saw palmetto’s efficacy with BPH but may also open the door to saw palmetto as a potential deterrent to prostate cancer.

The second study examines the role that DHT, 5-alpha-reductase, estrogen, and SHBG play in the pathogenesis of BPH. This study not only examines saw palmetto extract’s 5-alpha-reductase inhibiting actions, but also explores the efficacy of urtica (nettle) root in BPH treatment (14). As men age, their ratio of estrogen to testosterone increases, making it important to inhibit the effects of estrogens, SHBG, and DHT. While saw palmetto protects against prostate enlargement caused by DHT, nettle root is required to inhibit the proliferation of prostate cells in response to estrogen and SHBG. For this purpose, it appears the methanolic nettle root extract that is more effective than the former ethanol extract.

Nearly all of the studies conducted in the last 20 years (including over 20 double-blind, placebo-controlled) have reported improvements in BPH symptoms with use of this fat-soluble extract of saw palmetto, and most of these improvements were statistically significant. One article reports that a number of studies “have suggested that the extract can partially relieve troublesome problems – such as difficulty urinating and frequent urination at night caused by a swollen prostate gland, a fairly common malady among men over age fifty (15).

Now, let me thwart ALL claims of saw palmetto and its competition at the same receptor site as T acting as a potential receptor-site blocker. While this is PARTLY TRUE – the unfortunate problem with this blanket statement is that you MUST employ proper use of saw palmetto in the first place and this is a more localized effect. We will explore dosing protocols and how they MUST be adjusted in the PCT time frame as the series progresses with a comparative analysis to pharmaceutics.

Yet another benefit of the mineral zinc is the potential nourishment role it plays for the prostate gland keeping the gland as healthy as possible. The prostate contains a higher percentage of zinc than any other organ in the human body. If this mineral is not maintained at high levels, prostate enlargement and possibly cancerous growths may occur! BUT NEXT TIME, WE WILL DISCUSS HOW TOO MUCH ZINC CAN BE A BIGGER PROBLEM THAN TOO LITTLE – WOW, HOW COMPLEX, RIGHT?

Pygeum (Pygeum africanum)

This compound is thought to act in ways similar to saw palmetto. It is simply less widely studied.

Boron

There are opposing camps in the field of medicine on how useful prostate specific antigen (PSA) levels are as an indicator of diagnosing prostate problems, but when levels reach certain numbers, assumptions can start being made about the source of this elevation.

PSA < 4: Normal
PSA 4-10: Some indication of growth (potentially BPH)
PSA > 10: Indication of extreme growth (potentially Prostate Cancer)

When a number appears in the 4-10 ng/ml range, values can sometimes still be normal for certain individuals. In the labs I work at, the ratio of free PSA to that bound to alpha 1-antichymotrypsin is run when you get a value in this area to differentiate between benign and malignant prostatic diseases. Lower unbound MAY lend further support to malignant when compared to other prostatic diseases.

The aforementioned numbers are BY NO MEANS DIAGNOSTIC, but they can lend support to a diagnosis and rationale for concern should they be uncovered. They do tend us an offering of assessing response to therapy or progression of disease. Therefore, I recommend levels to be included on all men at baseline and in the post cycle time frame.

Still, there has been quite the multitude of proposed PSA hypotheses in relation to this ongoing saga of its usefulness. One such hypothesis involves PSA’s enzymatic ability to degrade extracellular matrix (structural support) proteins such as fibronectin and laminin (24). This action of PSA may promote tumor growth and metastasis.

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Another, perhaps more convincing, tumor-promoting action of PSA involves freeing insulin-like growth factor 1 (IGF-1) from its binding protein (BP-3), providing locally increased levels of IGF-1, leading to tumor growth (25).

Boron was first shown to be an essential nutrient for normal growth in chickens in 1981. Since then, numerous studies have found that boron is probably essential for normal production of steroids in humans, especially hormones involved in muscle growth and calcium, phosphorus, and magnesium metabolism for bone growth and maintenance. Marketing hype of the 1980’s in a sports supplement world approached this supplement wrong in its usefulness for athletes – claiming it to do all but go to the gym for you – leaving bodybuilders no choice but to abandon this nutrient in their quest for hugeness.

Fast forward 20 years - Cui and colleagues from UCLA showed that men with the highest intakes of dietary boron reduced their prostate cancer risk by 54% compared to men with the lowest boron intake (26). Studies on mice earlier showed that expression of IGF-1 in tumors was reduced by boric acid. Mice PSA levels dropped by an average 87%, while tumor size declined by 31.5% average. While dosing equivalents would translate to 6-15 mg to mimic the mice studies, the one done on humans used a much smaller dose to see improvement. While this nutrient may not do the major things purported in supplemental form to increase testosterone levels, if used appropriately, it can find itself playing a beneficial role in the post-cycle period.

Dosing parameters AND the “cycle within a cycle” rationale for Boron use will be discussed in the next article of this series. It would be particularly useful if ratio of borato-1,2-diaminocyclohexane platinum (II) (BDP) + boric acid solution were known, the components within boron thought to be responsible for its prostate benefits.

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Originally Posted by dinoiii

ERECTILE DYSFUNCTION ALLEVIATION

Yohimbe (Pausinystalia johimbe)

Yohimbe is the only botanical to boast FDA approval as a remedy for ED. Ironically, in spite of this unusual government approval for an herb, U.S. research on yohimbe’s effects on human males is still in its infancy. The active substance is yohimbine, an alkaloid in the bark of the tree of the same name (Paustinystalia johimbe), a native plant of tropical West Africa. The inner shavings of the bark act as a stimulant and aphrodisiac. The tree, which grows predominantly in Gabon, Nigeria, and the Cameroons, grows from 20-50 feet tall, and has leaves from 3-5 inches in length. The seeds are winged.

Pharmacologic properties of this indole alkaloid, is a alpha-2 selective antagonist. It doesn’t have what I would call an established clinical role, but theoretically, it could be useful in autonomic insufficiency by promoting neurotransmitter release through blockade of presynaptic alpha-2 receptors. An easy way to remember the autonomic control over penile function is through the following pneumonic:

 Parsympathetic = Point (Erection)
 Sympathetic = Shoot (Ejaculation)

It is perhaps evident why it is suggested that yohimbine aids male sexual function, but lets look at the evidence. Yohimbe is traditionally used by many Bantu-speaking tribes in a matrimony sacrament. It is used in mating rituals that have been known to last for up to 10-15 days (Holy BeJesus, is it a wonder it has obtained such a wonderful reputation). It has been used for 70 years as a treatment for both male and female sexual difficulties. Although yohimbe enjoys a reputation as an aphrodisiac among traditional practitioners, modern scientists have not been able to prove any effects on sexual drive in humans. The herb has been shown to increase sexual arousal and performance in male rats, but the effect in human males is yet unsubstantiated.

Yet, one study from Rhode Island showed that yohimbe increases blood flow to the penis. In clinical trials, the active ingredient in the herb was tested on men impotent for less than two years. An improvement rate of 81 percent was reported for those who took a moderate dosage of the active ingredient for one month. More than 60 percent of the men who had experienced only partial erections and had failed at normal intercourse at least 50 percent of the time experienced fuller, longer-lasting erections and overall improved sexual function.

Earlier studies reported 70-85 percent “good to excellent” results with impotent patients. In the 1980’s, a highly regulated landmark Canadian study showed that the active ingredient in the herb could be a significant aid for restoring potency in impotent diabetic and heart patients. This widely reported study purported a success rate for serious impotency cases of 44 percent.

In a 1994 Italian study, impotent inpatients were followed for eight weeks. Half received active tablets of yohimbe, half received placebos. The yohimbe group showed a 71 percent positive recovery rate; the placebo group showed a 22 percent recovery. You may think that perhaps this implies something more about the essential etiology (or be a potential weakness shining through form the study) in that 22 percent, however when the placebo group was given the yohimbe tablets, their success rate climbed to 74 percent! Coincidental?

In an additional 1994 double-blind study, eighty-two men with erectile dysfunction had a high incident of diabetes and vascular disease underwent a thorough evaluation. After one month of treatment with a maximum of 42 mg oral yohimbine hydrochloride daily, 14 percent of the men experienced full restoration of sustained erections. Twenty percent reported a partial response, and 65 percent reported no improvement. Only three men reported a positive effect from the placebo group. Not impressive results, but still statistically significant.

Yohimbe can be taken in capsule or liquid forms. Pure yohimbine hydrochloride (despite luxurious claims of marketing) requires a doctor’s prescription. You may see yohimbe in a health food store or on an on-line supplement site in bark or extract form, but some of these may or may not have yohimbine in them. A standard dose is 15-20 mg per day, but higher doses, up to 42 mg, may sometimes be necessary. The effects of the herb, unfortunately takes two to three weeks to manifest themselves. The trick here is that much of your PCT time frame may have elapsed and any erectile dysfunction may have subsided in this same time frame offering rationale to question when you should initiate therapy if at all.

I would find the answer a little more gray. I would opt out of use of this product for about 3 weeks into post-cycle time. If, at that time erectile capabilities continue to manifest, yohimbe supplementation or yohimbine therapy can be considered.

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Originally Posted by dinoiii

ANTIHYPERTENSIVES

Blood pressure tends to be one of the larger concerns for some while on cycle. The following supplements, while unable to discuss them all here mimic many drugs of the various pharmaceutic classes and can be used to get the blood pressure back in line with baseline.

Supplements that can act as Diuretics

Hawthorn Berry
Vitamin B6
Taurine
Celery
GLA
Vitamin C
Potassium
Magnesium
Calcium
Protein
Fiber
Coenzyme Q10

• One potential caveat here is that if concominant use of cell volumizers is being employed, use of the aformentioned set of items may best be avoided.

Supplements that can act as Central Alpha Agonists

Taurine
Potassium
Zinc
Celery
Sodium Restriction
Protein
Fiber
GLA/DGLA
Vitamin C
Vitamin B6
Coenzyme Q10
Garlic

Supplements that can act as Direct Vasodilators

Omega-3 fatty acids
MUFAs (omega-9’s)
Potassium
Fiber
Garlic
Flavonoids
L-arginine
Taurine
Celery
Magnesium
Calcium
Soy
Vitamin C
Vitamin E
Coenzyme Q10
ALA

Supplements/Foods that can act as Calcium Channel Blockers

ALA
Hawthorn Berry
Celery
Vitamin C
Vitamin B6
Magnesium
NAC
Vitamin E
Omega-3 Fatty Acids (EPA and DHA)
Calcium
Garlic

Suplements/Foods that can act as Angiotensin Converting Enzyme Inhibitors (ACEIs)

Hawthorn Berry
Garlic
Seaweed
Tuna, Sardines
Bonito Fish (dried)
Pycnogenol
Casein
Hydrolyzed Whey Protein
Sour Milk
Gelatin
Sake
Omega-3 Fish Oils
Chicken Egg Yolks
Zein
Dried salted Fish
Fish Sauce
Zinc
Hydrolyzed Wheat Germ Isolate

Supplements/Foods that can act as Angiotensin II Receptor Blockers (ARBs)

Potassium
Fiber
Garlic
Vitamin C
Vitamin B6
CoQ10
Celery
GLA and DGLA

Supplements/Foods that can act as Beta Blockers

Hawthorn Berry



While it is obviously impossible to cover all the aforementioned agents in an adequate light, there are a few worthwhile notes to make on a few within this class of agents.

Hawthorn Berry

Hawthorn berry is an herb that was used by the ancients to treat sleep and digestive problems. Modern studies indicate that it may also lower blood pressure and cholesterol, dilate the coronary arteries, reduce the incidence of irregular heartbeat, and otherwise combat hypertension, cardiovascular disease, and related ailments.

The versatility of this supplement is something that I offer the first nod to it. As I noted above, one of its modes of action is that it acts as an ACE inhibitor; that is, it works by inhibiting the angiotensin-converting enzyme that would otherwise cause constriction of the arteries. Hawthorn berry also contains various flavanoids, which have effects similar to beta blockers, calcium channel blockers, and diuretics. It contains rutin, magnesium, chromium, catechin, and several other phytochemicals, all of which work to combat high blood pressure.

Celery

Back in the nineteenth century, celery was considered a delicacy – an exotic and expensive vegetable to be served only at fancy dinners in specially-designed celery dishes. You could actually purchase celery gum and celery soda, and the Sears & Roebuck catalogue sold a celery elixir as a treatment for nervous ailments. Although celery’s popularity plummeted when it became cheap enough for everyone to afford, recent findings about its health benefits are liable to make it much more interesting.

In studies with animals, a component of celery oil called 3-n-butyl phthalide reduced blood pressure significantly. In a Chinese study, blood pressure fell significantly in 14 of 16 hypertensives who were given celery.

We don’t now all the ways celery can help us, but we do know that it contains a substance called apigenin, which among other things, helps lower blood pressure. Celery also acts like a diuretic or ACEI, helping rid the body of excess fluid, which may be the one way it reduces elevated blood pressure.

CoQ10

A relatively recent randomized, double-blind placebo controlled trial reported on the efficacy of CoQ10 in the war that rages on between 76 men and women with isolated systolic hypertension. For 12 weeks, the patients were either given 60 mg/day of the CoQ10 or a placebo. At the end of 12 weeks, the patients taking the CoQ10 showed a mean reduction in their systolic blood pressure by approximately 18 points (9)!

Garlic

Multiple reports have shown that both fresh garlic and garlic supplements can slightly lower total cholesterol and triglyceride levels (10). An article in the prestigious Journal of Hypertension examined the results of seven randomized, placebo-controlled studies on garlic’s effects on hypertension (11). The authors of the study found that garlic supplements, in the dose of 600-900 mg/day (which is roughly equivalent to two to three cloves of fresh garlic), reduced systolic pressure from 7.7 to 11.1 points and diastolic pressure by 5.0 to 6.5 points.

Taurine

This amino acid gets the dubbing as the amino the body doesn’t use to make protein. Instead, it circulates freely throughout the brain, retina, and heart muscle. Studies have shown that taurine can lower blood pressure and heart rate, while decreasing irregular heart rhythms and the symptoms of congestive heart failure. In a study of nineteen people with hypertension, giving each person 6 grams of taurine per day for 7 days reduced the systolic pressure by 9 mm Hg and the diastolic by 4.1 mm Hg (8).




SPECIFIC DOSING PARAMETERS NEXT TIME!

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Originally Posted by dinoiii

CHOLESTEROL/DYSLIPIDEMIA-MODIFYING AGENTS

The most predictable and universal effect of oral AASs, and one that has stimulated considerable research, is a decrease in the HDL fraction of cholesterol. The HDL-C2 fraction and accompanying A1 are most affected. The fall in HDL cholesterol is shortly preceded by increased activity of hepatic triglyceride lipase activity (HTLA), leading to the hypothesis that the decline is due to induction of HTLA. T and androstenedione also lower HDL. In contrast to the oral AAS, ND is not clearly associated with a decrease in HDL. In addition, AASs often increase the LDL cholesterol fraction, thus the combined effect is an increased LDL/HDL cholesterol ratio. Since a low HDL cholesterol and elevated ratio are risk factors for cardiovascular disease, the possibility that athletes and medical patients have an increased risk for cardiovascular disease has been considered.

Androgens have been implicated in myocardial infarction, atrial fibrilation, stroke, pulmonary embolism, hypertension, cardiomyopathy, sudden death and other disorders associated with the cardiovascular system; however, there is NO uniform hypothesis or mechanism that unites these observations. An autopsy was conducted on nine males who died suddenly while consuming high doses of AASs. A myocardial infarction was demonstrated in only ONE case; thus, except for the temporal relationship between AAS consumption and sudden death the mechanism for sudden death is not known and apparently does NOT involve infarction. The many ways in which AASs might influence the cardiovascular system have been reviewed.

Now, a caveat of the aforementioned material must be noted. There is a few pieces of literature that suggest that T actually LOWERS LDL and Lp(a). These studies have since been refuted and were not done with examination of typical dosing parameters used by bodybuilders during cycle.

Either way, it is most often exhibited that the cholesterol levels return to normal with cessation of the AAS, but there have been reports of a particular cycle beginning a cascade of detrimental lipid events, the pathogenic models of which are quite complex and for that reason remain beyond the scope of this article. Should you, however, become one of these latter reports, we will discuss the two most commonly suggested supplemental protocols for correction of various scenarios – described in “primary goals” that follow.

PRIMARY GOAL: LOW HDL CORRECTION

Niacin (Vitamin B3) + My Anti-Flush Protocol

The niacin or nicotinic acid form of vitamin B3 has been known to be an effective method for improving blood cholesterol levels since the 1950s. In the 1970s, the famed Coronary Drug Project demonstrated that niacin was the only cholesterol-lowering agent to actually reduce overall mortality (this information has since been updated with the advent of other agents).

-------------PHARMACOLOGIC SCIENCY STUFF--------

Nicotinic acid reduces plasma VLDL by inhibiting VLDL synthesis (20-80% over 1-4 days); it markedly decreases plasma triglyceride levels. As the substrate, VLDL concentration is reduced, the concentrations of IDL and LDL also fall, thereby reducing plasma cholesterol levels. HDL levels increase significantly.

The precise mechanism of inhibition of VLDL synthesis is unclear. Lipolysis in adipocytes is inhibited, reducing the major source of fatty acids for hepatic triglyceride biosythesis; VLDL catabolism is increased by an elevation in the activity of lipoprotein lipase; and a slight decrease in hepatic cholesterol synthesis is observed.
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Niacin typically lowers LDL cholesterol levels by 16-23 percent while raising HDL cholesterol levels by 20-33 percent. While niacin is available in the form of a prescription (Nicobid, Nicolar – discussed in latter parts of this series), it is likely a lot cheaper in the supplemental form, but the dose must be ramped up accordingly.

Niacin is available as a pure crystalline niacin and in sustained- or time-released preparations. Because of the significant risk of liver toxicity, sustained-release niacin should be AVOIDED, especially with the use of C17 alkylated orals! Contrary to the preachings of certain authorities, “no-flush” brands are neither synonomous nor homologous with the phrase “sustained-release.”

Inositol hexaniacinate yields slightly better results than standard niacin but is much better tolerated in terms both of flushing (the #1 side effect) and, more important, long-term side effects (hyperglycemia, GI disturbances, peptic ulcers, renal effects with elevated plasma uric acid levels, and macular edema).

Inositol Hexaniacinate (also referred to as hexanicotinate) is a special form of niacin composed of six nicotinic acid molecules bound to and surrounding one molecule of inositol, an unofficial member of the B vitamin group. Inositol hexaniacinate has been shown to exert the benefits of niacin without flushing or other side effects. It has been used in Europe for over 30 years not only to improve cholesterol levels but also to improve blood flow in the treatment of intermittent claudication and Raynaud’s phenomenon. Double-blind studies have verified the beneficial effects of this form of niacin in these peripheral vascular disorders.

While a third form of niacin is widely available, the aforementioned two offer the best cholesterol-modifying effects, whereas niacinamide is useful in arthritis and early onset type I diabetes. We will explore the dosing parameters of the protocol in subsequent parts of this series.

PRIMARY GOAL: HIGH LDL REDUCTION

Red Yeast Rice

The red yeast (Monascus purpureus) fermented on rice has been used in China for its health-promoting effects for over 2000 years. This yeast is the source of a small group of compounds known as monacolins that can lower cholesterol levels by blocking a key enzyme in the liver. In fact, the cholesterol-lowering drug Mevacor, the trade name for the compound lovastatin, also known as monacolin K, one of the key monocolins in red yeast rice extract.

The marketing of Cholestin (an extract of red yeast fermented on rice, standardized for monacolin content) as a dietary supplement in the United States has caused quite a controversy since 1997. Because it contains a natural source of a prescription drug, the FDA and the maker of Mevacor, Merck, tried to prohibit the sale of Cholestin and other red yeast rice extracts as a dietary supplement. The FDA’s ruling against Cholestin was temporarily reversed in March 1999, but two years later the FDAs ruling was upheld. Nonetheless, many red yeast rice products remain on the market.

These products, like their prescription counterparts, clearly are effective in lowering cholesterol levels. Over twenty clinical trials conducted in China involving thousands of subjects have shown red yeast rice extract to effectively lower high blood cholesterol levels by roughly 20 percent while raising protective HDL cholesterol by about 18 percent. A study conducted at the UCLA Center for Human Nutrition under the direction of David Herber, MD, has also demonstrated positive results. The double-blind, placebo-controlled study consisted of 83 healthy subjects with a cholesterol level between 200 and 239 mg/dl. Subjects were treated with 2.4 g of red yeast rice extract (Cholestin) supplying 9.6 mg of monacolins per day or a placebo. Both groups were instructed to maintain a diet of 30 percent fat with less than 10 percent saturated fat and less than 300 mg of cholesterol. On average, cholesterol decreased in the Cholestin group from 254 to 208 mg/dl by eight weeks, with no change in the placebo group.

While these results sound pretty good and from the outside looking in offer seeming support for this compound, the post-cycle time frame is NOT the time to employ potential use of this type of product.

First, it is a huge strike with those trying to use it with liver protectants post-C17 alkylated products. Liver enzyme elevations are reported as the number one side effect (3.4%). While this may not be a concern in the normal circumstance, the post-cycle period remains a unique time of recoup for all body organs – the liver perhaps having endured the biggest beating. Second, the development of muscle pains – perhaps indicative of a rare, but serious side effect known as rhabdomyolysis, are clearly evident in a few select cases (1%) of the general population. It is difficult to discern between post-workout DOMS and actual muscle pain due to this condition.

Red Yeast Rice like other statin drugs reduces the levels of Coenzyme Q10 at an alarming rate. With already depleted levels in many bodybuilders, this could play the role of a significant detriment to the well-being and attempts at regaining homeostatic environments seen prior to the cycle’s initiation. Niacin products at a dosage of 500 mg three times per day potentiates the effects of Red Yeast Rice and if employing either, it is strongly advised to avoid concurrent therapy. Interestingly enough, I will report a case of hepatic sides in an unknowing post-cycle patient using a Multi-Vitamin (containing Niacin products) and self-medicating with Red Yeast Rice later in this series. In addition, there are far too many drug-herb interactions – perhaps beyond the scope of this article to discuss, but it is wise to discuss the use of this product with your own examining physician if you are taking ANY prescription medications. I personally strongly advise AGAINST use of Red Yeast Rice at any point on or around a cycle.

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Guggulipid

Guggulipid is the resin or sap from Commiphora mukul (the mukul myrrh tree). The mukul myrrh tree, which grows in India, is really more of a shrub. As early as 1971, the positive effects of guggulipid (also known as gugulipid, guggul, and guggulu) on cholesterol were reported by Kapoor and colleagues in the proceedings of the Seminar on Disorders of Lipid Metabolism, held in New Delhi, India.

The active ingredients in guggulipid appear to be two plant sterols called Z-guggulsterone and E-guggulsterone. In elegant study by Singh and colleagues, these two steroids were shown to increase the uptake of LDL cholesterol by the liver. This, in turn, significantly lowers the LDL cholesterol in the bloodstream. Guggulipid has been shown to lower both LDL cholesterol (by about 12 percent) and triglycerides (by about 15 percent). Some studies have even shown some HDL improvement with guggulipid.

Guggulipid is used extensively in Ayurevedic medicine. Ayurvedic medicine uses drugs extracted from herbs, as well as diet, meditation, and exercise to treat disease. In India, guggulipid is sold as a drug, whereas in the United States, it is available in health-food stores. The typical dose of guggulipid is 25mg three times per day with meals. This changes considerably in PCT.

Most people have no side effects with guggulipid. There are a few cases of reported mild nausea, diarrhea, and headaches. Generally, these mild sides resolve with continued use. If you choose to use guggulipid, I think it is essential for you to let your doctor know. While it appears that the literature on guggulipid is solid science, the studies have typically been small. It is possible that guggulipid has side effects that have not yet been determined. We will see how this pans out in practice in the next part of this series.

Policosonol

Policosonol is a mixture of fatty substances isolated and purified from the wax of sugar cane (Saccharum officinarum). Policosonol has exceptional clinical documentation demonstrating efficacy, safety, and tolerability in lowering cholesterol and triglyceride levels. The clinical studies have included comparative studies versus conventional cholesterol-lowering drugs (i.e. – lovastatin, pravastatin, simvastatin, gemfibrozil, and probucol). In these studies, policosonol in dosages ranging from 5 to 20 mg per day has resulted in significant improvements in cholesterol and triglyceride levels, with effects typically noticeable in the first 6-8 weeks of use. At a daily dosage of 10 mg of policosnol at night, LDL cholesterol levels dropped by 20-25% within the first few weeks of therapy. At a dosage of 20 mg, LDL levels typically dropped by 25-30%. HDL cholesterol levels typically increased by 15-25% after only 1-2 months of use. The combined LDL reduction and HDL increase produced dramatic improvements in the LDL-to-HDL ratio.

In addition to its effects on cholesterol levels, policosonol also exerts additional positive effects in the battle against atherosclerosis (hardening of the arteries). It prevents excessive platelet aggregation without affecting coagulation (WHICH MAY PROVE VERY PROMISING DURING A CYCLE AND AFTER), prevents smooth muscle cell proliferation into the lining of the artery, and exerts good antioxidant effects in preventing LDL oxidation and subsequent arterial damage.

Great news for bodybuilders! This compound was not available in the United States until very recent as it is manufactured in Cuba. Alternatively, there is a suspect version of it that has been available from Natural Factors out of Canada.

Fish Oils / Various Other Sources of EFAs

This will be discussed at length during dietary discussions of article series.

Lecithin

All quality studies attempting to show cholesterol-lowering effects have simply NOT PANNED OUT! I would avoid this product in reduction of cholesterol levels for this rationale.



So, you may point out that I seem to be against cholesterol as the culprit of disease based on my Cholesterol Controversy series. I see it more imperative to keep in mind here that changes in cholesterol values during a cycle are variants from baseline through exogenous introduction of hormonal byproduct. It is an attempt during PCT to regain homeostatic balance and following your baseline levels of lab work to this point is IMPERATIVE!

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Originally Posted by dinoiii

PSYCHIATRIC EFFECTS

I am indifferent to this topic. I find the psyche imperative to discuss with the use of something potentially psychotropic. Most people I am familiar with DO NOT experience remarkable psychiatric effects while receiving AASs, although some report a general sense of well-being and invigoration – more likely induced by the way they are “supposed” to feel. AASs have been used to treat depression with VARIABLE results (27, 28) and with LESS efficacy than tricyclic antidepressants.

The hypothesis that T promotes aggressiveness in males is NOT supported by very many adverse reports arising from studies of T as a male contraceptive. Furthermore, supraphysiologic doses of T enanthate (600 mg/week) administered to healthy males for 10 weeks did NOT produce significant changes in mood or anger inventories, or in an observer mood inventory administered to spouses of significant others (29). A similar study reported marked hypomania in 2 out of 56 subjects (30), roughly the incidence of hyomania in the general population.

One study of AAS users found NO significant mood disturbances (31), however, reports of serious behavioral and psychiatric sequelae including aggressiveness, hostility, and even homicide associated with AASs are increasing (32, 33, 34). A structured psychiatric interview of high-dose users found a high incidence of aggressive behavior, affective syndromes, and psychotic symptoms (35). A double-blind, fixed-order, placebo-controlled study of the effects of placebo, 40 mg of MT, 240 mg of MT, and placebo withdrawl for 3 days each on mood and behavior in healthy, non-AAS users revealed both positive (euphoria, energy, sexual arousal) and negative (irritability, mood swings, violent feelings, hostility) mood changes during high dose MT (33). In addition, 1 of 20 subjects developed acute mania. The possibility that higher dose users develop an addiction with physical dependence and a withdrawl syndrome has been proposed (36).

Fortunately, there are some inferences that can be made at this time. The psyche is quite the strange beast. The variability of results is very representative of the potential variation – however, the inclusion of incidence rates being as low as they are would lend me to believe the psychiatric effects are self-induced in many cases should they show up – again, because it is perhaps an appropriate time for select individuals to act out because it is expected of them while on cycle. The addiction and physical withdrawl is, however, a very real subject even in placebo research (steroids aside), which is why I acknowledge it. The aforementioned paper on dependence and withdrawl only used 8 subjects, so I find it hard to make generalizations of the population as a whole. Further research is certainly warranted.

The case for the addition of a supplement here to offer placebo alleviation is perhaps warranted – but I will forego discussion at this time outside of stating take your pick: Kava, Melatonin, Valerian, Gotu kola, St. John’s Wort, 5-HTP, DLPA, and SAMe. None really stand out and some may be detrimental in the post-cycle period. A couple of these products find different uses and will be discussed with that in mind later in this series.

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Originally Posted by dinoiii

CELL VOLUMIZING AGENTS

Current preaching from various “authoritative” groups suggests the necessity of cell- volumizer inclusion. There is NO data that supports this anywhere, but I really have NO data to refute it either. So I will add a quick blurb on why they suggest it. Of the dozen or so “creatine cocktail” products on the market for this purpose, low-dose brands may not be as effective during PCT as good old creatine monohydrate. This is because the newer products don’t seem to cause as much inter-cellular water retention and bloating, which, post-cycle, is desirable in order to keep as much muscle as possible.

As I have stated, I do NOT refute the potential need for such concoctions, HOWEVER the rationale seems a bit stale and I will introduce some tricks for my recommendations of use that coincide with diet and exercise (PART VI of this series: Lifestyle Modifications). There is a bigger picture when including these such drinks that will become more apparent the further along in this discussion we go.

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FAT LOSS AGENTS

Interestingly enough, the aforementioned authoritative groups also claim that subsequent use of certain fat loss agents would be ideal during the post cycle time frame. At the same time, these groups have stated in the past that both items classically considered “cutting” agents should NOT be used concurrently with cell volumizers. HUH?

Actual data that acknowledges their concurrent use can allow us to make some inferences as to how we can employ these items. If aloud to use together or if would better be left until the POST-PCT time frame is unclear as there remains a paucity of research regarding the post-cycle time frame.

It can be deduced that re-partitioning agents show more promise than either stimulants or thyroid support in the immediate aftermath of AAS cessation. Why do I make this claim, especially versus the use of thyroid agents? Well, first, while it is accurate to say that both Free T4 and TSH levels are either unchanged (low normal) or DECREASED, and oral agents show DECREASES in plasma levels of BOTH T4 and T3. It must be noted that there is usually a concurrent proportional decrease in TBG. That being said, the administration of AASs is NOT associated with hyper- OR hypothyroidism.

At the same time, AASs increase the basal metabolic rate, although if the rate is calculated per gram of LBM, there is NO change (23). Insulin resistance and diminished glucose tolerance are reported with a couple 17-alkylated AAS, but not with esters of T or nandrolone. Your chances of regaining control of partitioning of nutrients may potentially be more quickly corrected with use of these agents. They will be fully addressed throughout latter sections of this series.

There are four supplements I find necessity to introduce here that fall within this category and each will be explored MUCH further as this series unfolds.

ColeusForskolii (standardized for forskolin)

Forskolin, a diterpene derivative, has cardio-protective and positive inotropic effects action in the heart (i.e. – it helps increase the force of heart contractions). It also acts as a vasodilator that lowers blood pressure and prevents platelet aggregation (formation of blood clots – will explain further below).

Some researchers believe forskolin to promote lean body mass by stimulating adenylate cyclase and cyclic AMP (cAMP) levels, which has the potential to enhance lipolysis and fat burning. cAMP causes a cascade of biochemical events that enhances body metabolism, thermogenesis, and provides mechanisms for controlling body composition and lean body mass. Despite the thyroid activity you will see below, for various reasons forskolin actually tops the list of repartitioning agents.

--------------------BIOCHEM BREAKDOWN------------------

TRIPLE ACTION

Lipolytic Activity:
Forskolin stimulates adenylate cyclase enzyme to increase cAMP levels activating protein kinases which phosphorylate the active form of hormone sensitive lipase to stimulate the release of fatty acids from body adipose tissues

Thyroid Stimulating Activity:
TSH activates adenylate cyclase in the membrane of thyroid cells, which in turn elevates cAMP and eventually leads to thyroid hormones being released which may also contribute to its ramping up metabolic rate. Forskolin replaces TSH at the beginning of this cascade to start the metabolic series of events in motion.

Thermogenic Activity:
cAMP mediates the mobilization of stored energy (the breakdown of carbohydrates in the liver or triglycerides in fat cells). This path is normally begun through the action of catecholamines which are decreased at the end of a cycle. Forskolin adequately acts as a replacement in the right doses.

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Recall that I suggested forskolin as a repartitioning agent versus thyroid stimulating. Again, this categorization is more based on its multitude and versatility of effects. One such effect is on the musculoskeletal system. Forskolin stimulates cAMP, a mediator of the relaxation of smooth muscle. Forskolin can offer accumulation of cAMP provided the proper dosing parameters which in turn increases nitrogen retention. This means that elevated cAMP levels help preserve or even INCREASE lean body mass while increasing lipolysis.

Other metabolic effects of AAS worth noting are adipose tissue response and electrolyte discrepancies. Adipose tissue contains ARs, and biopsies performed after a course of AASs reveal a marked decrease in lipoprotein lipase (LPL) activity. Perhaps, it can be seen why Forskolin would be beneficial here. This effect will actually work in your FAVOR in the long run when we discuss lifestyle changes, particularly diet later on.

Lastly, excessive doses of AAS result in modest increases in blood pressure due to salt and water retention (see discussion on blood pressure above). With adequate control of blood pressure our first concern, we can use this to our advantage. Forskolin, once again plays the role of hero. By increasing cAMP, which mediates vasopressin, it has an effect on the epithelial cells of the distal portion of the convoluted tubule of the nephron of the kidney. This augments resorption of water independently of solutes, resulting in concentrating the urine and concominant dilution of the blood serum with water retention by the water.

WOW – we solved the case of a place where a repartitioning agent actually plays the role of a cell volumizer. And, this is just the beginning.

Fenugreek (Trigonella foenum graecum L.; also known as "methi")

Fenugreek seeds have a long history of use in Ayurvedic medicine for the treatment of diabetes and heart disease. Scientific studies have shown that fenugreek-seed powder can lower glucose levels and improve a person’s cholesterol profile. We’ve seen how these can be positive effects in the PCT. It should be noted that the seed is far more effective than the ground herb ORALLY, however, one must question whether this is due to the 4-hydroxyisoleucine component that gets the acclaim or the fact that the seeds are comprised of 50% fiber which slows digestion and the postmeal rise in glucose.

Of potential additonal benefit, there is a purported increase in LH that some circles talk about these days. This simply does NOT have research backing and I do NOT find rationale to recommend its use in this way.

Colosolic Acid

Colosolic acid, known also as Regulin, is an extract from the leaves of Lagerstroemia specious L., a Philippine plant. Filipino and Japanese scientists have researched its effect on glucose levels, and it is a promising herbal supplement.

Colosolic acid has an insulin-like effect and has been described as a “phyto-insulin.” Both animal studies and human trials have found it to be safe and effective in lowering glucose levels. It has an advantage over insulin, in that it can be taken orally, whereas insulin must be injected.

A Japanese study conducted in 1998, tested colosolic acid on 23 subjects with glucose levels of 110 mg/dl, which is at the high end of the normal range. The subjects received either a placebo or three standardized Regulin tablets three times daily (after meals) for four weeks. The total daily dose of colosolic acid was 0.16 mg, or 160 mcg. Glucose levels declined in most patients.

7-keto DHEA

While closely related to its DHEA precursor, it is purported to offer no conversion to testosterone or estradiol and the potential detriments that are associated with it due to its downstream nature in steroidogenic pathways. There is NO evidence, however, that it has muscle mass increasing potential. The scary part to me about this (yeah, I have read the ads regarding its body comp potential) is that one study showed that it may actually have the opposite effect. The compound was given to 18 healthy men and a placebo to 6 men, aged 18-49, over an eight-week period. At the end of the study, testosterone levels were ACTUALLY SLIGHTLY LOWER in men taking the 7-keto. Despite, its potential promising effects shown in the immune system enhancement, memory, and fat loss research, I am VERY WARY of recommending this supplement in the immediate post cycle time frame secondary to the lack of exploration it may have on T levels.

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Originally Posted by dinoiii

SUMMING IT UP

So what about eurycoma? What’s the latest on chrysin? Ipriflavone and 7-Methoxy products have some benefit, no? How bout avena sativa or muira puama, or even sarsaparilla? There are over 60 compounds that likely would find some benefit in supplemental form that I simply have not had time to cover here or they will make appearances later in this series. EFA’s and EAA’s make the nutritional adjustments category and macronutrient rationales (seen in part VI), AT and ATD products are further engaged in the IN PRACTICE portion of the PCT supplements section (part III).

And can't you use some of these items during cycle? YOU MUST BE PATIENT.

As always if questions arise about things, feel free to comment below.

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Originally Posted by dinoiii

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