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PCT: A Clinician’s View PART III Post-Cycle Supplements: In Practice

- article originally published on-line on February 10, 2006

Dana Houser, MD, MHSA, CISSN

Author's Note: If you have yet to visit the PRIMER or PARTS I and II of this series, please do so at the following addresses before proceeding.


INTRODUCTION

One of the more feminine-like qualities I possess is the daily ritual of perusing through the “Living/Today” sections (title = dependent upon area of country I am in) of the newspaper to find my horoscope. Is it an act that holds much bearing on my life? Well, not exactly. It just seems to preach about a life better than mine – well, that is roughly 90% of the time. Ten percent seems like its right on the money and the “correct” ones tend to come in spurts – yesterday and today falls in the ten percent.

Yesterday: A dream compels you. If it weren’t so lovely, you would
feel like a slave to its ruthless demands. You focus on the delicious
possibility, so nothing you do feels like work.

Today: Challenge conventional attitudes – your fresh thoughts are
needed. You shine in the eyes of family and friends. Now, what
must you do to impress yourself?

2 excerpts from Holiday Mathis of
Democrat & Chronicle (Rochester, NY)

The dream simply begins with the PCT: ACV series which has received a lot of attention for me. I am lucky that it really is a passion in expressing my thoughts on such a topic. I feel this could be a never-ending book. The challenging of conventional attitudes (if not already apparent) will come fast and furious during this installment. I am actually not 100% impressed yet though. The latter part of the year will potentially offer that peace.

Last time, we looked at the various theoretical models implying how they may impact the construction of a post-cycle dietary supplement regime. Today, we see how these items (extracted straight from the paper onto which they have been hypothesized) translate into the real world. While dosages and the like are considered here, a true undertaking of application of these doses to various cycles will be looked at more in-depth in part VII of this series.

[Author’s note: No particular supplement is being marketed in this article as all of them. I have zero financial interest in any of the supplements that follow. In the same sense, I do NOT use ANY manufacturer’s brand name products in the paragraphs that follow – rare in this industry].


SUMMARY OF STEROIDOGENIC THEORY

Keeping the science to a minimum (there’s plenty in the paragraphs and sections that follow), it is imperative that we revisit the multiple pathways of testosterone action in recap-summary formation as to better establish the forthcoming real-world results of adequate post-cycle supplementation.

Normal Steroidogenic Testicular Synthesis Pathway (> 95%, Complete):
LH --> stimulate Leydig Cells of testis to produce Testosterone (primary pathway in males)

Normal Steroidogenic Adrenal Synthesis Pathway (< 1%, Incomplete):
ACTH --> stimulates Zona Reticularis Cells of adrenal gland to produce Testosterone (primary pathway in females, secondary pathway in males)...keep in mind that 90% of DHEAS comes from Adrenal secretion for later discussion, however. Cortisol will take on an indirect role here as well later.

Normal Steroidogenic Peripheral Conversion Synthesis Pathways (< 4%, Incomplete)

Inactivation Pathway:
Testosterone --> hepatic oxidation & conjugation / renal excretion

Amplification Pathway (prostate / skin, 5-10%):
Testosterone --> 5-alpha-reductase --> DHT --> Androgen Receptor

Direct Pathway (muscle):
Testosterone --> Androgen Receptor

Diversification Pathway (brain / bone, 0.1%):
Testosterone --> Aromatase --> Estradiol --> various metabolic pathways --> Estrogen Receptors (i.e. - E1, E2)

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ANTI-ESTROGENICS

(1) Aromatase Inhibitors

EVIDENCE-BASED EFFICACY: Unfortunately, studies performed by individuals without vested interest are NON-EXISTENT!!! Some wonderful hypotheses have been constructed, however, and on paper, they are not without merit – but my curiosity got the better of me as to how serum lab values would respond to use of various items suggested last time. While this in-house study is still underway, preliminary data suggests that the serum changes seen are those of average 3-fold increases in estradiol and subsequent increases in testosterone are NON-existent.

Choose-your-own Adventure style
Two-fold introduction to the model:

Step 1a) Decrease Aromatase --> Subsequent transient increase in T [If you want to reproduce results of classically-defined research, you can stop now, otherwise Go to Step 2a]

Step 1b) Decrease Aromatase --> Subsequent transient decrease in E [If you want to reproduce results of classically-defined research, you can stop now, otherwise Go to Step 2b]

Step 2a) Prior Affinity for AR leaves new T no where to go [If you are frustrated, you can return to path 1b and see how that adventure ends, otherwise make your way to Step 3a]

Step 2b) Decreased E --> Decreased SHBG [If you are frustrated, you are likely not alone, to see the demise of this pathway, move on to Step 3b]

Step 3a) Newly Increased T lends itself to become Free T (can overwhelm to increase SHBG oputput with prolonged output) – normally, this may be good but now, you continue negative feedback, no HPT axis recovery [SUPPRESSION = UNSUCCESSFUL PCT]

Step 3b) Decreased SHBG --> Increased Free E and Free T normally, this may be good but now, you continue negative feedback, no HPT axis recovery [SUPPRESSION = UNSUCCESSFUL PCT] - author’s note: this decrease in SHBG is actually a transient effect, after an average of 2.5 weeks of use, SHBG seems to super-compensate offering higher levels of bound hormone product. This model needs to undergo further study.

FORMS & DOSAGES: Without evidence-based backing, I am unable to recommend a dose at this time.

POTENTIAL SIDE EFFECTS / INTERACTIONS: AT/ATD are strong cytochrome P450 3A4 inhibitors (Ki values < 0.2 microM via in vitro human microsome studies). 3A4 is the workhorse of the P450 system. It accounts for 30% of P450 activity in the liver and 75% of the P450 activity in the small intestine (wait a minute – this is where ATD-type supplements are absorbed). Because so much P450 activity is due to 3A4, it comes as no surprise that 3A4 performs the bulk of oxidative drug metabolism in humans. This makes 3A4 arguably the most important human P450 enzyme to understand. Until the mid-1990’s, the literature included references to 3A3or 3A3/4. It is now understood, however, that 3A3 is not a separate P450 enzyme but a transcript variant of 3A4. Subsequently, the list of drugs and supplements that are metabolized by 34A IS CONSTANTLY GROWING! 3A4 being a high-capacity/low-affinity enzyme if inhibited means you get spill-over of the drugs to the low-capacity/high-affinity subset [namely in the enterocytes of the gut (recalling the high percentage of 3A4 activity in the gut): 2D6, 2C9, and 2C19]. In English, this means you have the potential for immense toxicity in other drugs metabolized by this cytochrome enzyme.

I will center our discussion here on the supplements that have inhibited metabolism when concurrently used with AT/ATD preached about as classic adjuncts during PCT. In the late 1990s, several 3A4-related casualties occurred, and the drugs were removed from the US market by manufacturers. These cases are reminders of the potentially serious nature of 3A4 inhibition.

INTERACTION #1: Red Yeast Rice (RYR) – a classically-described HMG Co-A reductase inhibitor and also anti-inflammatory and down-regulator of LDL receptors has the potential to cause Rhabdomyolysis (see my For the Love of Science and Medicine, Part II article for some clinical studies for evaluation) and extreme hepatotoxicity. I have already stated in Part II and previous articles/posts that RYR has absolutely NO business in a PCT regime following a C17 alkylated PH/PS/AAS. RYR coupled with either of the 3A4 inhibitors AT/ATD potentiates the aforementioned effects, so I amplify my response to the nth degree and ask with use of AT/ATD-containing products, you fully omit this item.

INTERACTION #2: Hawthorn Berry – a classically-described blood pressure modifying agent and this is attributed to its calcium and beta-blockades as well as its ACE inhibition and diuretic action. This rather safe supplement on its own with a great track record becomes a different animal when combined with 3A4 inhibitors. It can actually drop your blood pressure to a level that would in itself be dangerous. The key here is that if you opt to throw this compound in solely at the time of cessation of PH/PS/AAS that may have elevated your blood pressure – a decline of more than 25% at such a rapid rate can be deadly!

INTERACTION #3: Any sympathomimetic agent. While better avoided in the first place during PCT, people have considered certain agents that act through various andrenergic grounds and they too become MORE potent with AT/ATD.

CAUTION: Nolvadex, a commonly-puported “must-have” by many authorities during PCT. This is an obvious display of their ignorance and blatant disregard for drug-drug interaction as Nolvadex (discussed at greater length in part IV) is metabolized through the 3A4. Now, in addition to people starting at dosing parameters as high as 40mg (which is a highly unnecessary dose even for the heaviest of cycles) with a 7-day half-life, you have increasing toxic levels in addition to what you have already put together. Retinopathy or liver toxicity anyone?

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(2) Estrogenic Channeling Agents

Indole-3-Carbinol (I3C)

EVIDENCE-BASED EFFICACY: I have written extensively in various posts on my support of this compound versus its DIM metabolite as well as any other compound in the post-cycle realm from the category of “dietary supplement.” Perhaps the single-most important mechanism of action of I3C is modulating estrogen metabolism. That’s right, tell your friends – ALL ESTROGEN IS NOT CREATED EQUAL. Estrogen receptors are located on the surface of virtually every type of tissue in the human body. Guys, you too, are not off the hook as this applies to you as well.

The body modifies (metabolizes) estrogens through two mutually exclusive pathways, which lead to compounds with dramatically different biological activities. Estradiol is the primary estrogen in circulation (as the example used above in Diversification Model) and one of the most active. It is metabolized to a number of other chemicals, all with some degree of estrogenic activity.

Key here, are the enzymes 2-hydroxylase and 16-alpha-hydroxylase. Several years ago, scientists hypothesized that a preference towards the 2-hydroxylase pathway and the subsequent generation of 2-hydroxyestrone (2-OHE1), results in less toxic metabolites in the circulation, which was subsequently gone on to support a decreased number of breast cancer outcomes if this were the dominant pathway (later, this proved true for prostate cancer as well). It was also around that same time that the hypothesis of greater estrogenic metabolism via the 16-alpha-hydroxylase enzyme would yield greater amounts of the more potent 16-alpha-hydroxyestrone (16alpha-OHE1) and a larger number of estrogen-dependent cancers would likely be the result.

Summary of ORDET study of 2000 (always nice fancy acronyms)
Participants: 10,000 Italian women
Duration: > 5 years
Measured Items: Diet, other breast cancer risks
Findings: Increased level 2-OHE1:16alpha-OHE1 at beginning of study associated with less risk of breast cancer development.

This simply set precedent, mind you – although there is a 1% risk for men to develop breast cancer, posting this study is merely the landmark to establish the importance of greater 2-OHE1:16alpha-OHE1 ratios being desired for decreased estrogen-sensitive cancer risk. This is very important information to someone embarking on post-cycle supplementation.

Summary of Prostate Cancer Study
Although there was a failure to achieve statistically significant results in this study, elevated 2-OHE1 urinary levels indicated a decreased risk of prostate cancer, whereas an increased 16alpha-OHE1 urinary level showed an increase of prostate cancer 2-times that of men with the highest levels of 2-OHE1.

I3C modulates these pathways shifting the conversion of estradiol metabolism to favor the 2-hydroxylase pathway and the subsequent 2-OHE1:16alpha-OHE1 ratio is INCREASED, which correlates with a decreased risk of various estrogen-sensitive cancers. A potential caveat worth further exploration is the increase in production of yet another estrogen exhibited by some studies (4-hydroxyestrone – this is very potent). These increases were NOT significant, however, and as you will see and have seen in my various posts, are put out by people with vested interest in other products. There are multitudes of studies that actually show a concurrent DECREASE in 4-OHE1, so the mixed results tend to leave me questioning those trying to prove their various products superior. Catch my drift?

In addition, and certainly not something studied, but the data seems to suggest shifts from the more potent (2-OHE1) to less potent (16alpha-OHE1) in a time when there is the potential for increased conversion (and this goes out to all of my aromatase-inhibitor-loving friends) – namely, during the post-cycle period would also contribute to a shift in dose-response curves to the right (and that is for my pharmacologically-inclined friends). We’ll see in the pharmaceutic exploration (parts IV + V) that this is NOT the entire picture – unfortunately, I can only address these items one by one in a certain time allotment.

FORMS & DOSAGES: 200mg to as high as 400mg has been studied and based on available evidence, this is what I would be hard-pressed not to suggest at this time. There is no upper-limit established, but even while in the post-cycle realm, I would beg you to adhere to a max of 400mg per day as this is simply what has been supported to date.

POTENTIAL SIDE EFFECTS / INTERACTIONS: Although it may seem obvious that a substance consumed over 1000s of years by millions worldwide is inherently safe, it has been challenged recently by those with vested interest in its metabolite DIM. I have expressed my concern at the challenges DIM supporters have offered and it is just plain bad science. Numerous cell culture, animal, and human studies have demonstrated I3C’s safety and tolerability, along with its targeted ability to SUPPRESS estrogen-receptor-sensitive (breast, cervical, and important for this discussion – prostate) cancer growth (sorry Dr. Z), and induce programmed cell death in a variety of tumors, including those associated with breast, prostate, endometrial, leukemia, and colon cancers.

As an aside, the cytochrome P450 enzymatic system discussed above in the AT / ATD section within both the liver and intestinal track is actually STRENGTHENED by use of I3C – something that could prove especially beneficial to C17 alkylated users.

CAUTION: Be careful of “research” supporting concurrent use of DIM – usual vested interest is a hand-in-hand with the funding of such studies.

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PRO-TESTOSTERONE

DHEA

EVIDENCE-BASED EFFICACY: Although DHEA is promoted as a miracle supplement that can do everything from bolstering flagging libido, controlling weight, and improving mood to preventing or treating many of our most lethal diseases, there is LITTLE or NO evidence that it can do ANY of these things in humans. Most of the research to date has been done in animals, and human studies involved only small numbers of volunteers. Still, some of the results have been intriguing and hold promise that DHEA may eventually live up to some of its hype. SUPPLEMENT MANUFACTURERS HAVE MADE “EVENTUALLY” NOW!

I, for one, am sick of this supplement! Because the studies are scant, I will discuss the ACTUAL science and practice evidence that is known. DHEA circulates primarily in the blood as DHEAS, a sulfated version which is NOT, in itself, biologically active. When blood tests for DHEA are done, the test results do not usually discriminate between the 95% that is DHEAS and the 5% that is DHEA. Radioimmune assay of saliva, however, can be used to measure the concentration of the biologically active hormone, DHEA. Most not having this done really have ABSOLUTELY NO BASIS FOR INGESTION of this supplement AS THE SULFATED CONCENTRATION TELLS THEM NOTHING USEFUL. Sulfatase and Sulfokinase concentration tests are currently in the planning stages of development which may give us a better idea of serum conversion data between the reservoir DHEAS and active transformed byproduct DHEA.

FORMS & DOSAGES: DHEA marketed as a nutritional supplement is available in tablet, capsule, and cream forms. The usual recommended dosages range from 5 to 25 mg a day. Originally, DHEA was sold mostly as a non-prescription weight-loss aid. In the late 1980s, the FDA ordered that DHEA be classified as an unapproved drug that could be obtained only by prescription or participation in a clinical study. In 1994, it was reclassified as a nutritional supplement that could be sold in health food stores and other outlets. When it came under fire again during 2004’s Anabolic Steroid Control Act, I was pulling for it to actually be canned if any prohormone product was to go. Unfortunately, the cockeyed truly ANYTHING-BUT-SCIENTIFIC COMMUNITY known as legislators and lobbyers alike fought for its safety versus other compounds – well, if that doesn’t explain why government has little, if any, business in dietary supplement legislation, I am not sure what does. Alas, we live in an age where science seems to mean so little these days. And so I digress...

POTENTIAL SIDE EFFECTS / INTERACTIONS: DHEA may spur the growth of hormone-dependent cancers of the breast in women and prostate in men. Animal studies have found that it may also raise the incidence of liver cancer, but it is not known if humans face the same risk.

Dinoiii’s tip(s):
I DO NOT BELIEVE DHEA to have a true place in dietary supplementation in the first place, especially within steroidogenic pathways in the post-cycle time frame.

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Tribulus Terrestris

I, unlike others before me using bad research questioning its efficacy, like this supplement in the post-cycle domain, especially when we will see some problems with hCG in the next part of this series (always consider concurrent pharmaceutics and rationale). I know what anti-trib propaganda will suggest and I have covered a partial retort in my “Tribulus Terrestris: Worthless or Unjustifiably Chastized” article as well as my PCT: ACV II article, so I will not add to that argument at this time.

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Nettle (Urtica dioica)

EVIDENCE-BASED EFFICACY: Traditionally, this agent was used to treat hypertension throughout much of Europe. It has recently been the focus of many pharmacological studies (in vivo) designed to determine the nature and extent of its beneficial effects.

As previously discussed in this series, globulins like SHBG actively inhibit the level of free testosterone by binding to it, thereby rendering it biologically inactive. Research has found, however, that nettle extract has greater affinity for SHBG than does testosterone. As a result, SHBG binds more readily to constituents of the nettle extract, successfully counteracting its effect and thereby increasing the level of free testosterone. What an exciting incidental finding! Though this is not the only positive rationale for its use nor perhaps even the most important – health-wise in the post-cycle period for bodybuilders.

What is known by many in Europe as the “Nettle Effect,” shows some stunning biological ramifications. For example, researchers in Italy – within a series of in vivo studies determined that nettle has direct positive effect on cardiac action. In their study, they found they found that when pre-contracted endothelial tissue is injected with nettle extract, it elicits vasodilation. The researchers concluded that nettle can produce hypotensive responses through a vasorelaxing effect. This suggests that nettle can improve the symptoms of angina and reduce objective measures of myocardial ischemia in men with coronary artery disease.

As I discussed in the last article of the PCT: ACV series, nettle root also may benefit prostate gland health. In Germany, nettle has been used for decades in the treatment of BPH (discussed later in this article and the last of this series). DHT is proposed to be one of the contributing factors to prostate growth (of course, under dictation of the evil step sister estrogen as you learned in the last part of this series). Much the same as its effect on testosterone’s binding to SHBG, nettle inhibits the binding of DHT to its receptor sites on the prostate gland.

FORMS & DOSAGES: Treatment of BPH: 600-1,200 mg daily. But for all testosterone fans desiring an elevation in free levels, multiple doses over the course of the day (considering half-lives, roughly 4 hours) may still offer convincing rationale proposed by one supplement company in its beta-version.

POTENTIAL SIDE EFFECTS / INTERACTIONS: Although allergic reactions to oral stinging nettle are rare, fresh nettles can cause a rash if they come into contact with the skin. Should a similar reaction start to appear at higher frequency in oral users, now would be the time with numerous supplements cropping up with this item in them in the post-ASC act of 2004. The oral does pose some minor gastrointestinal upset in some people but overall, it appears very safe.

Dinoiii's tip(s): I would advise AGAINST its use with non-steroidal anti-inflammatory drugs (NSAIDs, such as Aspirin, Ibuprofen, etc...) as it has the potential to enhance their effects which could subsequently lead to an upper GI bleed via NSAID-induced ulceration.

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I am just covering the major Post-Cycle Points regarding the next two minerals:

Magnesium

Post-cycle considerations here lie heavy in its primary role in enzymatic activation. It is second to potassium in terms of intracellular concentration.

Human Body concentration:
21-28 grams of magnesium

Intracellular Magnesium breakdown:
~ 60% in bone
~ 26% in muscle
~ 14% in soft tissue and body fluids

Potential Sources of Post-Cycle Magnesium Deficiency:
- Multi-Vitamin Use (namely, high calcium – always question the producers of a supplement that contain both calcium and magnesium)
- liver disease (especially concerning for increased number of C17 alkylated use)
- exogenous progestin use

Deficiency Issues to consider:
- heart disease
- high blood pressure
- insomnia + concurrent daytime fatigue
- mental confusion
- irritability
- muscle spasms / cramps
- loss of appetite ( + interesting sequelae that may follow)
- predisposition to stress (see later why this may expedite a particular reconditioning of ACTH)

Zinc

Although severe zinc deficiency is relatively rare in developed countries, this is NOT necessarily the case in heavily-trained athletes. It is believed that many zinc deficiencies go unnoticed and the number of zinc deficiencies is grossly underestimated leaving many athletes with a marginal deficiency. Zinc is in every body cell and is a component in over 200 enzymes. In fact, zinc functions in more enzymatic reactions than any other mineral. A couple of the associated effects of zinc deficiency worth noting in the peri/post-cycle time frame that may see benefit are testicular atrophy and male sexual function likely modulated by zinc’s role in testosterone production. Although testosterone is not the only hormone modulated by zinc to promote proper function. You can tack thymic hormones, insulin, and growth hormone on to that list and they all have important roles in proper post cycle runs.

One final thing – perhaps you have found yourself with some post-cycle acne. There are a few studies that support the use of zinc supplementation to fend this off. Subsequent testosterone regeneration that offers up an outbreak as well may very well be avoided.

Dinoiii’s Tip(s):
To all my multi-vitamin lovers: look to the back of your bottles – should you see concurrent listings for calcium, copper, iron, manganese, OR molybedenum alongside zinc as I have warned you of in my BodyOpus: Reloaded article, you could be robbing your body of this important nutrient – not a good thing coming off a cycle!

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ANTIOXIDANTS

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

EVIDENCE-BASED EFFICACY: This sulfur-containing vitamin-like substance plays an important role as the necessary cofactor in two vital energy-producing reactions involved in the production of cellular energy (ATP). Lipoic acid, while not considered a vitamin, is an accessory nutrient where a relative deficiency can occur in certain situations, PCT being one of them. It has a well-known antioxidant role.

The racemic mixture is an approved drug in Germany for the treatment of diabetic neuropathy (nerve disease). Several double-blind studies have shown supplementation with 300 to 600 mg daily does improve neuropathy thought to be attributed to its antioxidant properties (which also has shown positive results with compromised antioxidant defense systems in HIV/AIDS research with subsequent serum level elevations in vitamin C, gutathione, and T-helper lymphocytes). Within the diabetic literature, there is also great rationale to support its improvement in blood sugar metabolism, increase insulin sensitivity, improve blood flow to peripheral nerves, and actually stimulate the regeneration of nerve fibers. All of the aforementioned effects have certain tendencies to appear in some people on cycle and post, especially with increased work loads (increased weights with use of exogenous anabolic product).

What’s more? The liver is protected from free-radical damage (to a limited degree, of course) and promotes detoxification reactions. Preliminary studies suggest a possible role in the treatment of hepatitis and cirrhosis of the liver, but more clinical research is needed to confirm these effects.

FORMS & DOSAGES: For general antioxidant support, the recommended dosage remains a measly 20 to 50 mg. I think general antioxidant for a very well-documented, safe antioxidant dose centers more in the 100 mg dosage of the racemic. Diabetic neuropathy and liver disorders were shown to see efficacy at doses ranging from 300-600 mg daily (HIV/AIDS, this dose is cut in half and taken 3 times per day, therefore 150-300 mg three times per day). How can this data be extrapolated and applied to PCT? Concominant liver toxicity and muscle strain with oxidation warrants consideration in varying doses. There is a volume of distribution factor to consider here, however.

Low End of Liver Toxicity Continuum (non-C17 alkylated)
Racemic Mixture Dosing Parameters (general antioxidant):
< 180 lbs. 100-200 mg / 2 times daily
180 – 200 lbs. 200-300 mg / 2 times daily
> 200 – 220 lbs. 300-400 mg / 2 times daily
220 – 240 lbs. 400-500 mg / 2 times daily
240 – 260 lbs. 500-600 mg / 2 times daily
> 260 lbs. 600 mg / 2 times daily

High End of Liver Toxicity Continuum (C17 alkylated)
Racemic Mixture Dosing Paremeters (general antioxidant + Liver protectant):
< 180 lbs. 400-500 mg / 2 times daily
180 – 200 lbs. 500-600 mg / 2 times daily
> 200 lbs. 600-700 mg / 2 times daily (levels beyond this become increasingly less
cost efficient)
* Author’s Note: Please subtract Liver Protectant Additions for C17 alkylated if choosing additional liver protectants. Revert to non-C17 requirements.

POTENTIAL SIDE EFFECTS / INTERACTIONS: Generally regarded as safe, however, hypoglycemic reactions can occur. Due to blood sugar modifications, possible interactions are likely with other glucose modifying agents and this compound may be better left alone at the higher end of dosing.

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Carnitine

EVIDENCE-BASED EFFICACY: While touted as an agent with the potential benefit of aiding impaired fat utilization and energy production with the ability to transport long-chain fatty acids into the mitochondria, its efficacy in this domain has NOT been supported. It is likely that the science here suffers from the various attempts of applying it to oral supplementation.

Nonetheless, clinical research concentration still offers great support for several other items of importance, namely things worth considerable consideration in the post-cycle realm: cardiovascular disease, enhancing physical performance, improving sperm count and motility, cognitive research (namely, Alzheimer’s Disease and age-related senility), kidney disease, and hemodialysis. We will address some of these results from the literature.

For what is approaching the last 20 years, research into the area of cognitive function has proven itself quite significant. A normal reaction that occurs on a daily basis in humans at a copious rate, is one that sees the coupling of acetic acid and L-carnitine forming acetyl-L-carnitine (ALCAR). There are not many places that look into direct comparison of L-carnitine versus the acetylated version – so I am unable to offer estimation into how much more effective the acetylated version is, however, study design usually uses that rationale in attempt to support its use vs. the basic L form.

I don’t want to get heavy into the science on this one, but a minor delving into it is imperative to see what conclusions can be drawn and how aging research can be applied to PCT. ALCAR resembles the neurotransmitter acetylcholine (Ach) which is involved simply in memory and proper brain functioning. In various conditions, there is a decline in Ach utilization. The close structural similarity led researchers to explore the use of ALCAR in Alzheimer’s patients first, followed closely by the aging brain. Results have been extremely encouraging. Cognitive decline or loss of focus and attention is seen readily in post-anabolic use. A hypothesized rationale has TO DATE, not been offered, but I will offer a reason I think this to be the case.

There is some research showing that exogenous testosterone in the aging male leads to improved memory and shows wonderful replicability with Alzheimer’s patients, though it could unfortunately be eons before the FDA approves such an indication. I am willing to place money on the withdraw of exogenous testosterone and subsequent suppression of pituitary gonadotropins (namely LH in this scenario) to be at least, in part, responsible for what I officially dub the phenomenon of POST-CYCLE SENILITY! Now, it is transient in nature and certainly not to an Alzheimer’s, nor age-related senile senility level – but a true anecdotally-reported phenomenon with mental decline coupled with loss of focus in the post-cycle realm. It warrants true future exploration.

Cardiovascular side effects are not something new to the seasoned steroid user.

A Summary of Cardiovascular positives suggested in studies:

• CARDIAC SIDE of the coin: Normal heart function is critically dependent on adequate levels of carnitine. Spanning the huge spectrum of various heart diseases, an association can be made to true morbidity through impaired energy production and low carnitine concentrations. Such disorders as Angina pectoris, congestive heart failure, mitral valve prolapse, and even recovery from an acute myocardial infarction are offered hope through oral carnitine supplementation.
• VASCULAR SIDE of the coin: studies show average decreases in elevated cholesterol and triglyceride levels that span all domains. While recent research shows cholesterol may not be a huge consideration (please see my cholesterol controversy series), triglycerides continue to plague people’s lipid profiles.

FORMS & DOSAGES: All forms produced in capsules, tablets, and liquid. ALCAR, propionyl-L-carnitine, and L-carnitine. [Author’s Note: No studies have been performed on what is touted as “Carnitine Ethyl Ester” – recall from other posts, esterification is simply en vogue now and in this instance, HIGHLY UNWARRANTED – Good try though!]

Dinoiii’s Basic Research Translation Recommendations (clear-cut examples to follow in part VII):
• ALCAR: up to 2 grams per day during the entire duration of PCT for prevention of POST-CYCLE SENILITY.
• Propionyl-L-carnitine (PLC): 1.5-2 grams per day during cycle + PCT for both Angina pectoris and congestive heart failure (CHF)!!!
• L-carnitine: 500mg per day during cycle + PCT for heart attack (acute MI) and cholesterol prevention.
• L-carnitine: 1-2 grams per day with the use of progestin-derivative AAS.
• L-carnitine: 1 gram per day PCT for kidney disease + hemodialysis (which diuresis applies to bodybuilder’s of continued nephron – functional unit – strain).
• L-carnitine: 300 mg 3 times per day for liver protection (again, more support would likely lend itself for those involved with heavy C17 alkylated use).
• L-carnitine: 3 grams per day for a minimum of 4 months prior to cycle for potential low sperm count and decreased sperm motility.

Each Carnitine Conglomerate Plan should be individualized to the particular cycle and cannot be simply applied to all cycles by way of blanket statements. This ensures the inability of marketing such a supplement with success as I would call manufacturers’ bluff on the rationale supporting such a supplement!!! There are some other secret items you will have to wait for the book for as this is not the entire story, but I am giving up quite a bit for free.

POTENTIAL SIDE EFFECTS / INTERACTIONS: Synergistic effects (i.e. – cardioprotective, nephroprotective) shown to thwart side effects of classic chemotherapeutics demonstrating cardiotoxicity (namely, Doxorubicin and Daunarubicin) as well as EPO drugs in anemia and hemodialyzed patients. There are no adverse effects that have been demonstrated with either food derivatives NOR dugs.

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ACES

While there is a plethora of research I could easily apply to the Post-Cycle realm when talking about Vitamin A, Vitamin C, Vitamin E, and Selenium and their antioxidant role, it remains beyond the scope of this writing due to the extensive level of research and my not being able to do an adequate job in the space I have devoted to it. I will say that I think it imperative in the post-cycle realm to consider these items and NOT IN THE REALM OF A MULTI-VITAMIN offering too much potential for cross-reaction and subsequent deficiency (as displayed in detail in part II) at a time when deficiency is simply unacceptable.

[dinoiii]

HEPATOPROTECTANTS (Liver-Protectants)

N-acetylcysteine (NAC)

EVIDENCE-BASED EFFICACY: This natural-occurring derivative of the amino acid cysteine. Cysteine, glutamic acid, and glycine form the antioxidant glutathione. In PCT: ACV Part II, you learned of the evolution of this compound in post-cycle use and how the literature on acetaminophen didn’t necessarily translate into use within the post-cycle time frame. From PCT: ACV Part I, however, we can likely begin to see the unfolding of our game of dominoes.

There were 1,174 deaths (adjusted value based on autopsy) and in excess of 18,500 in the hospitalized realm associated with overdose of acetaminophen (Tylenol, paracetamol) in 2004. Overdose with acetaminophen is capable of injuring the kidneys, heart, and central nervous system, but its most pronounced effect happens with the liver as you saw in part II based on various metabolites. Brief recap: Ingestion of acetaminophen and its N-oxidation yields toxic metabolites (namely, N-acetyl-p-benzoquinone imine, aka NAPQI) that deplete liver glutathione stores and subsequently damage the liver. This action of NAC is QUITE SPECIFIC and has been mistranslated in the supplement world on a number of accounts. First, this specificity to acetaminophen OD is really attributed to overwhelming the 2E1 cP450 enzyme and in science speak this is solely a reaction that isn’t a terrible concern in human dosing. We challenge it, however, when going above the set daily upper-limit of 4 grams of acetaminophen and overwhelm it at 10 grams – much becomes dependent upon our inner abilities as either fast or slow acetylators as well ... But I am really trying to keep this as non-scientific as possible (the extreme science can be found in my upcoming book). What’s more is that extremely high doses are needed in the medical realm, and this is through IV infusion, not an oral capsule as many OTC supplements are sold!

Now, I know what you’re thinking. Nah Dana, I’m still taking my high dose self-prescribed acetaminophen. You just have not convinced. Ok, perhaps we can look at a bit more of the evidence-based data in attempts to do that (plus see in-house study below). I like NAC’s ability as an antioxidant, a free-radical scavenger – if you will. Heck; that is after all how it’s marketed. Preliminary human studies show it may not be as useful as less expensive antioxidants though such as vitamin C. Extrapolation from data on individuals with hereditary deficiencies of glutathione synthesis show better response to vitamin C (3 g per day) than to NAC (800 mg per day). The same may be true in normal individuals, though it obviously hasn’t been studied. There is evidence that NAC supplementation at higher dosages (> 600 mg) may act as a PRO-oxidant, however, the same caveat applies to many purported antioxidants – I just have supplied you with the value. One study found that NAC given orally to six volunteers at a dosage of 1.2 grams per day for four weeks, followed by 2.4 grams per day for an additional two weeks, it actually DECREASED oxidative stress by 83% and REDUCED glutathione concentrations by 48%! Until this issue is resolved, I would be hard press to recommend more than 600 mg per day in healthy individuals, and that number may be pushing the envelope a tad.

Curious how many people have done their homework here or simply assumed the role of a domino?

Other studies show minor support in the realm of bronchial and lung disorders, but terrible results when considering HIV/AIDS patients. It is probably needless to say that NAC has not been studied in the post-cycle realm (until this piece, of course – see below!).

FORMS & DOSAGES: I think adequate oral dosing (keeping in mind our upper limit established in the aforementioned paragraphs) hovers around 200 mg – up to (yet, not exceeding) three times per 24-hour period. This info is imperative to follow closely when in post-cycle phases.

POTENTIAL SIDE EFFECTS / INTERACTIONS: N-acetyl cysteine shows interactions with the following drugs: carbamazepine (Tegretol), nitroglycerine, and several classes of chemotherapy drugs. While this info may not seem important to you in the realm of bodybuilding if you are not on any of the drugs I just mentioned, keep in mind nitroglycerine behaves in a way similar to byproducts of arginine supplementation and the two are better left alone and not used concurrently. Potential side effects to develop with arginine and NAC include: headache (#1), nausea, vomiting, and other gastrointestinal symptoms.

[dinoiii]

SAMe (S-adenosyl-methionine)

I will not tell a lie! Anyone familiar with my writing understands that this is my absolute favorite hepatoprotectant and this is NOT unsubstantiated and I have absolutely no vested interest here as this is simply not marketed well – i.e. – there is simply no money in my bringing a product like this to the market as you can already get some VERY cheap brands (in my attempt to head off the potential boo’s and hiss’). The thing I like the most is that is has an impeccable safety profile. This is NOT something that can be said about a lot of supplements.

Pharmacology – SAMe is formed in the body already by combining the essential amino acid methionine to adenosine triphosphate (ATP). Over 50 biochemical reactions in the body draw upon this compound. It functions close with folic acid and vitamin B12 in methylation (addition of a methyl group – which is one central carbon atom with its outer electron shell requirements fulfilled with 3 hydrogen bonds – to another molecule, namely metabolites of steroid metabolism in this case) reactions. SAMe is many times more effective in transferring methyl groups than other methyl donors.

Shhh – I know a secret! SAMe is also required in the manufacture of all sulfur-containing compounds in the human body, INCLUDING glutathione (which we have spoken about at lengths thus far in its role within the liver – important for C17 alkylated users) and various cartilage components, INCLUDING chondroitin sulfate.

EVIDENCE-BASED EFFICACY: In extrapolating the data here, we visit SAMe’s positive effects in depression, liver disorders, migraine headaches, AND osteoarthritis – all of which are reported sides to a degree with PH/PS/ and certain AAS use.

My vote goes to SAMe as the most-effective dietary antidepressant (although admittedly, a strong argument could pit St. John’s Wort and this toe to toe and it would likely come down to the score card – you wouldn’t see a KO by any stretch of the imagination). Now, in studies SAMe has shown BETTER results than prescription antidepressants with less sides! There is more importantly, for our discussion, some hugely positive results in regard to relief of anxiety and depression associated with drug detoxification and rehabilitation. How does it do - become an effective antidepressant, that is? It increases levels of serotonin, dopamine, AND phosphatidylserine (wait a minute, can it too be anti-catabolic???). Serotonin and dopamine, in fact, see improved binding to their respective receptor sites.

Several liver disorders show phenomenal effect in response to SAMe therapy. These include: cirrhosis, Gilbert’s Disease/Syndrome (not incredibly terrible disease, I have it and my bilirubin levels have dropped since beginning use of SAMe – former elevations during periods of stress in my own serum levels are a thing of the past), oral-contraceptive induced liver damage (which may be data that extends across ALL progestin use – which obviates rationale for its use with certain PH/PS/AAS).

It doesn’t stop there! One of the absolute key functions of SAMe in the liver is the INACTIVATION OF ESTROGENS!!!!!!!!!!! Clinical studies have shown that SAMe is quite useful in protecting the liver from damage and improving liver function in conditions associated with estrogen excess – WHO DOESN’T SEE MY POINT??????? Admittedly, this estrogen excess is with oral contraceptive use, pregnancy, and PMS in the study sense, but application has proven interesting in my own in-house study here (see below).

SAMe has been shown to offer benefits in the treatment of more-severe liver disorders, including cirrhosis. One of the greatest risks of chronic liver diseases such as chronic hepatitis is liver cancer (hepatocellular carcinoma / hepatoma – being the worst case). Supplementation with SAMe appears to be very much indicated in these patients in the attempt to reduce the risk of liver cancer. Animal studies have shown a significant protective effect for supplemental SAMe against liver cancer in animals exposed to liver cancer.

SAMe has shown tremendous efficacy in the battle against osteoarthritis. A deficiency of SAMe in the joint tissue, just like a deficiency of everyone’s well-accepted glucosamine, leads to loss of the gel-like nature and shock-absorbing qualities of cartilage. As a result, one of the proposed mechanisms of pathophysiologic etiology of osteoarthritis is SAMe deficiency.

SAMe has been studied in a total of 21,524 patients in detailed clinical trials. In these studies, SAMe has demonstrated reductions in pain scores and clinical symptoms similar to those achieved with non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin, naproxen, and piroxicam. While these drugs are associated with significant risk of toxicity, side effects, and actual promotion of the disease process in osteoarthritis, SAMe offers similar benefits without the same risks of side effects. Can you imagine how this information can all be applied to bodybuilding lifestyles and the essence of weight-bearing issues with heavy poundages post-cycle (due to obvious strength increases and adjustment) or not?

FORMS & DOSAGES: SAMe is available in capsules and tablets. Commercially, it was brought to Europe in 1975, however it took 13 additional years for it to show up here in the United States. The recommended normal dosage is too low for someone post cycle. I recommend an enteric-coated 400 mg up to two times per day in the post cycle realm (this cannot be overstated in post-cycle time frame surrounding C17 alkylated products!). You may consider titrating up in dosing and there are interestingly enough no volume of distribution effects here to consider.

Don’t let your head spin in trying to figure out labeling. I’ll do it for you. SAMe is sold with added compounds for stabilizing the molecule and preventing degradation. These compounds include: tosylate, disulfate tosylate, disulfate ditosylate, and 1,4-butanedisulfonate (Actimet), and they’re usually written immediately after SAMe’s chemical name on the bottle (see dinoiii’s tip below).

POTENTIAL SIDE EFFECTS / INTERACTIONS: Individual’s with Bipolar Disorder (manic depression) should not take it. Why? It’s antidepressant effects discussed earlier could induce a manic phase. Be advised. Adverse effects are usually of the mild gastrointestinal variety (i.e. – nausea, diarrhea, etc...) which is why I recommend enteric coating as it tends to decrease these potential sides.

Dinoiii’s tips:
(1) Typically, the stabilizing compounds I mentioned earlier (tosylates, et al) weigh as much as the SAMe molecule itself. Consequently, a tablet containing 200 mg of SAMe disulfate tosylate contains ONLY 100 mg of SAMe. Most, but not all labels are likely to make this clear.
(2) Don’t let companies fool you here – there have been many independent lab testing done on various SAMe brands...if you ever have a question on a brand that matched up to label claims (only less than 50% do!) just let me know.

[dinoiii]

Silymarin

So, we see this term thrown about, but not too often do we hear, what in the world is this, but somehow, I am sure not many of you know (but your secret’s safe with me). I will allow you now to act smart in front of your friends free of charge with your silymarin knowledge. In short, silymarin is a fancy, shmancy name for a mixture of flavonoid components (i.e. – silybin, silidianin, and silichristine) from milk thistle. The concentration of silymarin is highest in the fruit, but it is also found in the seeds and leaves. Milk thistle extracts standardized for silymarin usually find their way into your favorite supplements at about a 70-80 percent concentration.

Fancy Shmancy, maybe. However, silymarin is at least ten times more potent in antioxidant activity than vitamin E and also increases the liver’s own antioxidant, glutathione (which we have spoken about at great lengths thus far in this series) by OVER 35%!

EVIDENCE-BASED EFFICACY: Positive effects have been seen with 70-80% concentration in treating several types of liver disease, including hepatitis and cirrhosis. The therapeutic effect of milk thistle extracts in these disorders has been confirmed by biopsy as well as by clinical and laboratory data.

Although milk thistle extract has shown benefits in treating acute and chronic viral hepatitis, the results with milk thistle extract are most impressive when looking at studies evaluating its effectiveness in alcohol- or toxic-chemical-induced hepatitis, which is why it applies readily to the post-cycle time frame. For example, in one double-blind study in workers exposed to toxic toluene and/or xylene vapors for five to twenty years, milk thistle extract (Thisilyn) was shown to significantly lower levels of AST and ALT, while significantly improving other blood measurements, such as platelet count, white blood cell count, and percentage of lymphocytes compared to other white blood cells (but it’s use can also create an inaccurate picture for clinician’s, so we must be wary in our question asking during history taking).

Even in cirrhosis of the liver, milk thistle extract has shown some benefits. Although not all studies have shown significant effects, in one controlled study the four-year survival rate was 58% in the milk thistle group compared to 39% in the control group.

There have been no studies to date examining the potential of milk thistle to treat gallstones through it’s ability to increase bile solubility (gallstones form when bile components fall out of solution). When there are drastic body re-composition events, namely fat loss – this is ABSOLUTELY AN IMPERATIVE POINT as gallstones have a tendency to readily form.

FORMS & DOSAGES: Milk Thistle is available as bulk and dried seeds, as tea bags, as a tincture, as a fluid extract, and as a solid extract in tablet and capsule forms. Extracts standardized for silymarin content are preferred as it is the component proposed to be responsible for the extract’s mechanism of action (recall bioflavinoid complex discussed earlier). There is some preliminary data to suggest combinations of Silybin, the key component in silymarin within milk thistle, and phosphatidylcholine would help aid absorption. It is too early to tell and the data available was thus far only published by those with vested interest, so I cannot say definitively. The regular version standardized should be good enough anyway – so why get fancy?

The goal of therapy here will be based on silymarin content. If using the dried seeds, a much lower dose is necessary to see positive effects of the compound.

POTENTIAL SIDE EFFECTS / INTERACTIONS: The earliest side noted is a looser stool (due to increase of bile output). Aside from that, it tends to be a rather safe supplement with a great track record.

If you are taking the following drugs: thyroid hormone, acetaminophen, butyrophenones, phenothiazines, phenytoin, and even alcohol, I advise AGAINST the use of milk thistle as it has a tendency to drive down efficacy of these agents.

Dinoiii’s tip(s):
(1) If loosened stool side effect occurs, it is a good idea to take some sort of fiber source (i.e.- guar gum, pectin, psyllium, and/or oat bran) with your milk thistle dose if it is desired to continue to use the product. This will help aid bile binding preventing irritation.

[dinoiii]

--------------------------------IN-HOUSE STUDY ---------------------------------

Houser, D. The Efficacy of Various OTC Hepatoprotectants in the Post-Cycle time frame following use of C17 alkylated PH/PS – a double-blind, placebo controlled look. (2004) [Unpublished to date-see below]

Study Group: 34 clients in Post-Cycle Therapy after the use of upper-limit dosing of various C17 alkylated PH/PS products. The breakdown of the in-house participants was as follows:

Group A: 15 Solitary M1T (Dosing Parameters: 20 to as high as 60 mg per day x 6-10 week cycles).
Group B: 7 M1T + MD (Dosing Parameters: 12 to as high as 30 mg per day of each x 4-12 week cycles).
Group C: 12 MD + MOHN (Dosing Parameters: 12 to as high as 20 mg per day of each x 4-18 week cycles).

Group A

Study Participants:
5 participants – 600mg NAC
5 participants – 400mg enteric-coated SAMe
3 participants – 600mg NAC + 400mg enteric-coated SAMe
2 participants – placebo-control

“Cliff-Notes” Summary: 4 of 5 participants in SAMe-only group and all 3 participants in NAC + SAMe group had an average 5-day faster return to baseline of AST/ALT elevations than NAC and placebo-control. The addition of NAC in the dual-coverage group seemed to offer no additional benefit without statistically significant results between the two. NAC + placebo-control groups saw no statistically-significant changes in AST/ALT levels. Results seem to suggest SAMe is superior, at least in the post-cycle realm, to NAC in returning transient LFT elevations to baseline INDEPENDENT of cycle length. The essential caveat was the unanswered question in regard is why one of the SAMe-only participants mimicked results of NAC and placebo. Author’s Note: A current follow-up series of serum studies in specific regards to this individual are underway as we speak in hopes of offering answers.

Group B

Study Participants:
3 participants – 600mg NAC
3 participants – 400mg enteric-coated SAMe
1 participant – 600mg NAC + 400mg enteric-coated SAMe
(Author’s Note: not enough participants in this arm for placebo-control)

“Cliff-Notes” Summary: Similar results to Group A were seen in this arm. The SAMe-only and SAMe + NAC participants saw an average 3-day faster return to baseline of AST/ALT elevations. The faster return to baseline of transient LFT elevations was again INDEPENDENT of cycle length. It is truly unfortunate that there was no ability to gain a placebo-control group here, but M1T + MD in a concurrent run was not one of the most popular cycles when these PH/PS products were still being marketed legally. With the support of the first and third arms of the study, some definite inferences can be made. It would appear that the SAMe inclusion is what offered aid in the post-cycle realm for expedited returns to baseline LFT.

Group C

Study Participants:
4 participants – 600mg NAC
4 participants – 400mg enteric-coated SAMe
2 participants – 600mg NAC + 400mg enteric-coated SAMe
2 participants – placebo-control

“Cliff-Notes” Summary: Once again, the SAMe-only and SAMe + NAC participants saw an average 8-day faster return to baseline (inferences about the strength of PH and subsequent elevation in transaminase can likely explain the difference 5 vs. 3 vs. 8 respectively for the three arms) SPECIFICALLY in cycles under 8 weeks. Cycles that extended beyond this time frame tended to exhibit results that were not statistically significant when compared with either the NAC-alone or placebo-control groups. Of note, 2 participants in this arm did NOT see LFT elevation (1 in NAC only and 1 in NAC + SAMe groups). This is likely to be attributed to one of two things: specificity to elevation to particular PH/PS run or irregularly low-level baseline LFTs (of which has not been explored to date due to lack of participant follow-up).

* Author’s note: All information gathered here was done prior to the October 2004 ban. Due to legal issues, follow-ups for replicability are thwarted by the Steroid Control Act of that year. The aforementioned 3-arm study will appear in an upcoming book with complete lab values verified by Quest Diagnostics reports.
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Summary of Hepatoprotectant Use in PCT: Despite certain supplement companies’ claims, the attempts to replicate NAC results in oral (PO) form have been less than stellar and shows these particular supporters simply either not doing their homework or just attempting to “kitchen sink” their products with a bell and whistle. You can get away with very cheap brands quality-tested, but it is imperative to be careful in choosing which brand to go with. Fortunately enough, many brands of SAMe have been tested independently and it would appear this to be the OFFICIAL dinoiii agent of choice at this time, especially post-C17 alkylated oral use.

Quality Dose: 400mg enteric-coated SAMe (keeping in mind concentration of stabilizers we learned about above) two times per day (bid) + Milk Thistle (dose accordingly).