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Kevin Levrone is among professional bodybuilders like Dorian Yates who have opened up about their steroid cycles and dosages.In an interview with Muscular Development Kevin Levrone outlined his first and second steroid cycles with specific details, which gives us great insight into what kind of compounds and dosages he used to build his physique up.Levrone went through only a handful of cycles before he ended up on the Olympia stage.It’s insane to think that within just a couple years of steroid use Kevin was already standing on stage beside Dorian Yates placing 2nd at the 1992 Mr. Olympia.Kevin Levrone story is one of the best examples in history of elite genetic response to steroids.[embedded content]Kevin Levrone’s First Steroid CycleKevin Levrone started his first steroid cycle at 24 years old, six weeks out of his first competition (the 1990 NPC Maryland State Championship).Kevin first steroid cycle was comprised of:During that went from 198 pounds up to 206 pounds six weeks later while simultaneously burning fat.[embedded content]Although we are only able to have a glimpse of what his physique looks like after that first cycle due to the limited number of available photos, we can get a fair idea of the kind of musculature he was displaying at that first show.When it comes to testosterone use (and steroids in general), an increase in fat-free mass doesn’t necessarily mean that the body weight is comprised of only contractile tissue.This is often overlooked and is evidently exaggerated in the clinical data on graded dose response to testosterone in healthy young men.Because of this, we need to speculate a bit on how much weight Kevin actually gained during this first cycle of actual pure muscle.Based on an 8 pound gain, the simultaneous drop in body fat, and Kevin’s body composition he showed on stage at that first show, we can surmise that he probably gained around 10 pounds of muscle during that 6 week cycle.Kevin Levrone’s Second Steroid CycleAfter winning the 1990 NPC Maryland State Championship, Kevin had some time to eat in a calorie surplus and actually have a full off-season before his next pro qualifier show.Kevin’s second steroid cycle is far more indicative of his genetic response to anabolics as his first cycle was only six weeks long and didn’t have as much leniency in regards to his calorie allotment.Kevin’s second steroid cycle was comprised of:That comes to 1700 mg per AAS per week for his second cycle.Despite that being a fairly aggressive second cycle, Kevin claims he has never experienced negative side effects throughout his entire career.This second cycle is what allowed Kevin to pack on 30 pounds of fat-free mass between 1990 and nationals in 1991.Kevin Levrone’s Contest Prep CycleFor contest prep Kevin would add in androgenic hardening agents and let the more water retensive drugs work out of his system.At the start of contest prep Kevin added in four amps of Winstrol per week, split into twice weekly administration (2 amps administered twice per week).Winstrol V came in 50-milligram amps, so his weekly Winstrol dosage was 200 milligrams.At four weeks out, Kevin dropped the Testosterone, Nandrolone and Anadrol.At two weeks out Kevin added in 20 milligrams per day of Halotestin tabs, and would go into shows on Winstrol and Halo only.Between 1990 and 1991, Kevin’s stage weight increased from 206 pounds to 236 pounds.A 10 pound stage weight increase per year I would consider a VERY successful off-season.[embedded content][embedded content]Kevin managed to put on 30 during his first off-season, and found himself on the Olympia stage placing second to Dorian Yates within 2 years of his first steroid cycle.[embedded content]Related

As more and more IFBB pros and past Mr. Olympia winners like Dorian Yates start to open up over social media about their steroid use, we have started to get incredibly detailed insight into things like their genetic response to their first steroid cycle.From a very early age, it was pretty obvious that Dorian Yates was different from the rest and had a hyper-response to training and anabolics.A lot of people look to Dorian Yates as the pinnacle example of “hard work beats talent” and how “genetics aren’t everything”.A bit of delusion has been created stemming from Dorian’s training philosophies whereby many have truly started to believe that you can just grind harder than the next guy in the gym and completely make up for lacklustre genetics.The reality is that Dorian actually has some of the most insane bodybuilding genetics of all time.His biceps were a bit average compared to the rest of him, but other than that there was literally nothing wrong with his genetics at all, and the reason he became Mr. Olympia in the first place was his incredibly superior genetics.This is what Dorian looked like prior to training.Dorian Yates After 6 Months Of Natural TrainingDorian stepped on stage for his first bodybuilding event only 6 months after starting training at 21 years old.This event was at the Temple Hotel across the street from the gym that he worked out at.This is a picture of him posing at that event at the Temple Hotel Birmingham in 1984.According to him, this is after 6 months of natural training.6 MONTHS!He’s already bigger than almost every single person you would see at your local gym who have been training years.After 9 Months of Natural TrainingAfter only 9 months of natural training, Dorian already looked like a bodybuilder and had surpassed 99.9% of the population who has been working out for years.I see guys on gear constantly who look much worse than this that have been cranking for years.This is not something that can be attributed solely to “hard work beats talent”.Dorian Yates’ Progress From His First Steroid CycleMoving forward to 1985, Dorian did his first steroid cycle to prepare for his first official bodybuilding competition, the Novice West Coast (England).This is what he looked like at that first show.At the Novice West Coast Dorian placed first and shortly thereafter went to the World Games in London and placed 7th.This is after his first cycle, which was only 18 months after starting training.Within a year and a half, Dorian had already packed on what appears to be upwards of 40-50 pounds of pure muscle.Dorian Yates’ First Steroid CycleQuoting Dorian from an interview he did on his steroid use, his first cycle was as follows:[embedded content]It was 1985.I was 23 years old and had decided to enter my first competition after a year and a half of training, in which I had made excellent progress.I knew the others who would be competing would be using gear, and I wanted to even the playing field.It was a very deliberate decision that I didn’t take lightly, and I did as much reading as I could first.At 23, I feel I was old enough.At that age, you are fully matured physically, you’ve reached your full adult height, and so on.Even though I hadn’t been training terribly long, I had already managed to develop my physique to a decent level.Looking back, I may have been able to win that contest without using anything.I did one six-week “building” cycle of 20 milligrams of Dianabol a day, which took me from 215 at 5’11” to 235.Those were the most dramatic results I ever saw from steroids.I took six weeks off the gear, then at eight weeks out from my contest I began using 15 milligrams of Anavar per day, as well as one shot of Primobolan a week, which was 200 milligrams.I competed at around 210-215 and won that contest.EFBB [Britain’s equivalent of the NPC] officials were there and convinced me to represent the United Kingdom the following weekend as our heavyweight at the IFBB World Games.I placed seventh, and competed with men like Berry de Mey and Matt Mendenhall, both of whom were the top amateur heavyweights in their respective nations at that time.– Dorian YatesDorian Yates Rate Of Muscle GrowthAt the 1985 show, we see Dorian displaying an insane level of progression relative to what he looked like in the Temple Gym photoshoot in 1984.There’s a reason he became Mr. Olympia in the first place, and anyone who wants to argue that his training intensity, workout split, and training past failure is the reason he made such ridiculous progress is delusional in my opinion.Dorian gained upwards of what looks to be 20-30 pounds of stage weight per year until he won the Olympia.Even on what many would consider baby dosages of gear, he still easily swept high level bodybuilding shows and gained muscle at an incredibly fast rate.You can’t attribute that progress to just “he trained harder than everyone else”.Related

After reviewing the molecular weight of some of the most promising SARMs developed, I theorized that they could potentially be prepared in a topical solution for hair loss prevention.As you probably already know, Selective Androgen Receptor Modulators (SARMs) are a class of androgen receptor ligands that bind to androgen receptors and exert tissue selective anabolic effects with a relative lack of androgenicity when compared to traditional anabolic steroids.The end goal of their continued development is more or less to create the ultimate anabolic agent that can completely offset tissue loss as a result of musculoskeletal degenerative diseases, with a complete absence of androgenic activity in the body.While certain SARMs are closer to reaching this goal than others, the perfect SARM has yet to be developed.However, that doesn’t mean that the SARMs currently developed cannot be leveraged in some capacity for a variety of potential applications.As alternatives to oral SARMs, topical SARMs may be a promising area of research in the fight against hair loss.This article highlights the reasons why I believe there is such therapeutic promise in topical SARMs for hair loss prevention.[embedded content]Table of ContentsRole Of Androgens In Causing Hair LossDespite there being a cascade of events that lead to hair loss, the presence of too many androgens is ultimately what causes follicular miniaturization.However, the effects of exogenous androgens on the human body will inevitably vary between individuals due to several dependant factors in this cascade.As a rule of thumb, raising androgen levels via exogenous androgens will generally initiate or accelerate hair loss for someone who is hair loss prone.Unfortunately, anabolic steroids will unavoidably bring along some degree of concurrent androgenic activity.Our natural endogenously produced steroids are not an exception to this, and the androgen load in the body needs to be addressed in some capacity to attenuate, or even reverse hair loss.Standard Treatments For Hair Loss: Finasteride And DutasterideFinasteride and Dutasteride are medications designed to treat hair loss by inhibiting the enzymatic process responsible for DHT production.This means that they are not anti-androgens that bind to androgen receptors, but rather they prevent the body from converting testosterone into the much more androgenic metabolite dihydrotestosterone (DHT) by inhibiting the enzyme 5-alpha reductase.A 5 mg dose of Finasteride per day will inhibit approximately 70 percent of the body’s systemic DHT, in comparison to 0.5 mg Dutasteride; which inhibits 90 to 99 percent of the body’s systemic DHT.For most individuals, androgenic activity caused by DHT will be minimized after Dutasteride serum concentrations have peaked in the body, as there will simply be barely any DHT left.However, even with a high dose of Dutasteride, scalp DHT levels may not be diminished enough to completely deprive the tissues of DHT, and there is a substantial concurrent spike in scalp testosterone levels as a result of the blockade created at 5-alpha reductase.Not only is there potential for residual scalp DHT, but you if you rely on a 5-alpha reductase inhibitor as a form of hair loss prevention monotherapy you will still have a significant amount of testosterone unaccounted for in your body that still has its own inherent androgenic activity.I’ve posted a video on this before, where I review my over one year long experiment with Dutasteride where I lowered my DHT to undetectable levels and increased my testosterone levels into borderline supraphysiological territory.[embedded content]The inherent androgenicity of testosterone was still substantial enough to progress my androgenic alopecia.In fact, I still had all the characteristics of androgenic activity:facial hair growthbody hair growth (albeit notably reduced, which is to be expected)high libidomorning wood and good erectile qualityhair lossIn contrast to 5-alpha reductase inhibitors, a compound that reduces androgenic activity in the scalp by effectively targeting the androgen receptors would be more efficacious in staving off further hair loss progression.This is what prompted the development of anti-androgens.Transgender Hormone Therapy (Male-To-Female) For Hair Loss PreventionDuring the process of male-to-female gender transitioning, one of the first things doctors would do is prescribe estrogen or an estrogen analog to crush endogenous testosterone levels while increasing feminine hormones.They may also introduce anti-androgens to the protocol to further reduce the amount of androgenic activity in the body.One of the side effects of gender transitioning via anti-androgen and estrogen therapy is significant scalp hair regrowth, and complete reversal in even some of the most extreme cases.In some instances, men with nearly slick bald heads have grown back pre-puberty heads of hair via this kind of protocol.While this is clearly the most extreme method of reversing androgenic alopecia, you can’t argue with the results it produces in individuals who feel the risk/reward is worth it, or simply desire to become more feminine.Certain non-steroidal anti-androgens that interact with androgen receptors are designed to compete with testosterone and DHT for androgen receptor binding, while other steroidal anti-androgens work through slightly different mechanisms, albeit still working around the biological target of endogenous androgens (the androgen receptor).For the sake of not overcomplicating this section with too much scientific jargon, I’m going briefly summarize the pharmacodynamics of the two most commonly used anti-androgens in the hair loss prevention community, and elaborate on how SARMs may stack up to them.BicalutamideBicalutamide is a non-steroidal anti-androgen that is recognized for its affinity to androgen receptors, thus preventing testosterone and DHT from binding and transcribing their effects in tissues.Bicalutamide is a highly selective competitive silent antagonist of the androgen receptor, and is often utilized in androgen deprivation protocols, both clinically and experimentally.A common feature of pure anti-androgens, such as Hydroxyflutamide and Casodex (Bicalutamide), is their relatively weak binding affinity for the androgen receptor, 50–100 times less than that of Testosterone [R].On paper, it doesn’t seem like Bicalutamide would be very effective at preventing hair loss because of its weak binding affinity.However, the typical prescribed dosages of Bicalutamide are high enough that so much of the drug gets into the system that it essentially overpowers testosterone and DHT for androgen receptor binding.The logic behind this protocol is basically that the drug is poor at what it is designed to do, and for it to work it needs to be dosed extremely high until there is just so much of it circulating in the body that it overpowers testosterone and DHT by sheer volume.The half-life of Bicalutamide is 5-10 days as well (depending on single vs. continuous dosing), consequently allowing serum concentrations of the drug to accumulate far more over time.By creating a blockade of the androgen receptor, bicalutamide prevents the negative feedback androgens would normally create via the hypothalamic–pituitary–gonadal axis (HPG axis) in men.As a result of this, luteinizing hormone (LH) spikes in the body as the body recognizes a need to produce more androgens.After LH spikes, the gonads produce more testosterone, and more of that testosterone 5-alpha reduces into DHT, as well as aromatizes into estrogen.150 mg Bicalutamide per day in men has shown to increase testosterone levels by 59-97%, increase estrogen levels by 65-146%, as well as increase DHT, SHBG and prolactin to a less significant degree.This significant spike in estrogen will often lead to estrogenic side effects during Bicalutamide monotherapy.Gynecomastia is a very common occurrence during Bicalutamide monotherapy.Cyproterone AcetateIn contrast to the non-steroidal anti-androgen Bicalutamide, the steroidal anti-androgen Cyproterone acetate works by suppressing testosterone production directly, as well as competing for androgen receptors.Cyproterone acetate is one of the first anti-androgens developed, but it is still one of the most effective to date for hair loss prevention.With that being said, it has also shown to be one of the most side effect ridden compounds used for this purpose.Cyproterone acetate was originally clinically deployed to “treat” hypersexuality and sexual deviation.It was also used to delay precocious puberty.When puberty begins before age 8 in girls and before age 9 in boys, it is considered “precocious puberty”.As cyproterone acetate was used both in full grown men as well as pre-pubescent children, the conflicting findings in its pharmacodynamics have led to differing conclusions on how it works in the body, but for the sake of this article being about full grown men preventing hair loss, we will obviously be evaluating the clinical data on full grown men.Cyproterone acetate causes a prompt drop in LH and FSH levels, and consequently a massive drop in testosterone levels.In a study conducted on healthy male sexual offenders, dosing 50 mg cyproterone acetate twice daily caused testosterone levels to fall to subnormal levels within 1 week [R].Cyproterone acetate has the highest anti-androgenic activity of any other clinically used progestin.Despite it having a fairly weak binding affinity when compared to DHT and testosterone, Cyproterone acetate works similarly to Bicalutamide in that it accumulates during daily dosing because of its 1.6–4.3 day half-life, and also is dosed high enough clinically to increase serum concentrations high enough to a point whereby it can effectively compete for AR via sheer volume.In addition, because Cyproterone acetate significantly reduces testosterone production (and by extension DHT production) via its progestogenic activity, there are less endogenous androgens for Cyproterone acetate to compete with for AR as it accumulates, consequently making it very effective at displacing androgens at AR and inducing systemic anti-androgen activity.Cyproterone Acetate Vs. BicalutamideSteroidal anti-androgens have largely been replaced now by non-steroidal anti-androgens clinically, but cyproterone acetate and spironolactone are still commonly used in the management of feminizing hormone therapy.Cyproterone acetate is more effective at reversing hair loss than Bicalutamide anecdotally, but also comes with a significantly elevated risk profile associated with its use.Maintaining Masculinity Vs. Your HairWhile oral anti-androgens certainly work to reduce androgenic activity in the scalp, they also will often cause a variety of undesired side effects.Aside from the actual health concerns in regards to hepatotoxicity, musculoskeletal degeneration, and more, the main thing we are going to focus on is the effect anti-androgens have on your literal manhood.Expectedly, anti-androgens can cause feminization, loss of libido, erectile dysfunction, as well as muscle and bone loss.Now, like I mentioned, non-steroidal anti-androgens like Bicalutamide are substantially better in this regard, whereby they will not cause musculoskeletal degeneration, will maintain relatively normal sex hormone levels, and do not have many of the drawbacks of steroidal anti-androgens [R].However, that doesn’t mean that they are ideal, as they can still throw off the balance of androgens to estrogens in the body and prevent you from improving your body composition.Anything inhibiting testosterone from binding to androgen receptors in muscle and bone and transcribing anabolic effects will get in the way of your body composition goals at the end of the day.Inhibiting DHT and testosterone from binding to androgen receptors systemically will also impede countless physiologic processes that are facilitated via endogenous androgens in the body.This isn’t a flaw of the drug necessarily, as it is doing exactly what it was designed to do.However, androgen deprivation does not complement most of our goals as men, nor does it complement our health and quality of life.We want androgen deprivation in the scalp only, with no alteration of our systemic hormones or health markers.Obviously this is easier said than done, or else we would already have a topical anti-androgen available that stays localized, has a higher binding affinity than DHT, and has no systemic absorption.This compound does not exist, so we have to make do with our current pharmacology and understanding of pharmacodynamics.Oral Anti-Androgens Vs. Topical Anti-AndrogensMany would question why we don’t just use Cyproterone acetate or Bicalutamide topically to achieve this.The reason why these fall short as topical treatments essentially boils down to the fact that their binding affinity is poor, and their success as anti-androgens is largely achieved via their accumulation in the body systemically.When it comes to topical treatments, we don’t want something with a week long half-life, as it will start to accumulate in the body and cause systemic anti-androgen effects.The ideal compound would be something that has a short half-life, a high binding affinity for androgen receptors, and acts as a highly selective competitive silent antagonist in the scalp exclusively.The closest we have come to this so far is RU58841, with CB-03-01 showing therapeutic promise as well despite having a much lower binding affinity.[embedded content]A compound that does not convert to deleterious metabolites systemically is also advantageous, as there will unavoidably be some level of systemic absorption with any molecule that is small enough to penetrate the stratum corneum after topical application.While current topical anti-androgens commercially available do work for some individuals, there are limitations to each which I have delved into before.There is no perfect treatment at the moment, but in this article I elaborate on something I feel is worth further exploration when it comes to creating a strong localized androgen receptor blockade with as minimal of a systemic impact as possible.How Anti-Androgens Are Related To SARMs For Hair LossAt the end of the day, how does this all intertwine with SARMs?The bodybuilding community, the hair loss prevention community, and the research between them actually intersects in many ways that are commonly overlooked.I first realized the therapeutic promise of SARMs in a hair loss prevention capacity when I saw someone stop their hair loss cold turkey with the SARM S4 and exogenous Estradiol.What many don’t realize is that non-steroidal SARMs like S4 were synthesized using the chemical structure of traditional anti-androgens like Bicalutamide as their backbone.The most promising SARMs exhibit binding affinities several times higher than these anti-androgens, and I feel are an extremely promising area of untapped research for hair loss prevention.Some SARMs at certain dosages have shown to be as anti-androgenic as compounds like Bicalutamide and Hydroxyflutamide, more anti-androgenic than Finasteride, but with the benefit of actual tissue selective anabolic activity in muscle and bone.[embedded content]Basically, some SARMs can prevent hair loss better than Finasteride, as well as traditional anti-androgens, all while allowing supraphysiological muscle growth.The reason this is possible is that most SARMs have much higher binding affinities than traditional anti-androgens and can be far more effective at competing with endogenous androgens for AR binding and activation.In addition, because they are tissue selective, once they bind to androgen receptors, they induce anabolic activity in muscle and bone with a relative lack of androgenicity in other tissues like the prostate and scalp.I detail how this works further in one of my older articles called “Do SARMs Cause Hair Loss? | Can SARMs Prevent Hair Loss“.Oral SARMs also lower SHBG and can have a suppressive effect on endogenous androgen production at high enough dosages (and even low dosages with some SARMs).Through this suppression, SARMs can lower the androgen load in the body even further.With long-term use, certain SARMs may suppress endogenous testosterone production enough that the use of estrogen alongside the SARM becomes a necessity if aromatization is no longer satisfactory to maintain healthy estradiol levels.This presents an interesting scenario whereby androgen levels can be crushed to nearly undetectable levels via a non-steroidal SARM, and the additional negative feedback provided by the exogenous estradiol being added to the protocol to maintain therapeutic estrogen levels.The end result of this is essentially a heavy duty anti-androgen protocol that can maintain significantly more muscle mass than what is possible via traditional androgen deprivation therapy.However, oral SARMs obviously have their limitations as suppression of endogenous androgens is going to result in decreased libido, drive, and overall masculinity.While many who use traditional anti-androgens don’t care about this as they simply want the most efficacious way to nuke their hair loss, there are going to be many individuals who want to minimize the systemic impact of any treatment they deploy to keep their hair.This is where I believe there is therapeutic promise in topical SARMs.Difference Between Topical SARMs For Hair Loss And Topical Anti-AndrogensSARMs and anti-androgens are both effective at inhibiting gene transcription via androgen receptor competition.By competing against endogenous androgens for androgen receptor binding, topical anti-androgens like RU58841 and CB-03-01 are effective at preventing hair loss completely for some individuals with mild hair loss, and moderately effective at providing at least a decent foundation of protection for some individuals with more aggressive hair loss.One limitation of topical anti-androgens is that they work in a dose-dependent manner, but can wreak havoc if they get systemic.As I showed earlier with Bicalutamide, the higher volume of drug present, the more difficult it is for testosterone and DHT to bind to vacant androgen receptors.With anti-androgens its not as simple as increasing the dose until it works though, as topical solutions will go systemic to some extent, and the more drug you introduce to your system, the more anti-androgen activity you will get systemically.For someone with aggressive hair loss, chasing the volume approach with topical anti-androgens to overwhelm the endogenous androgens present in the scalp may lead to significant systemic side effects before adequate androgen receptor competition to prevent hair loss is even achieved.SARMs on the other hand will have a negligible impact on endogenous androgen production when trickling into the system in trace amounts, and will not induce anti-androgen activity in muscle and bone even if a substantial amount of it does get into the bloodstream.SARMsAnti-AndrogensComparable Binding Affinity To Testosterone For Androgen ReceptorsSOMESOMETranscription Of Anabolic AffectsYESNOTranscription Of Androgenic AffectsMINIMIZEDNOSide Effects To Systemic IntroductionMINORMAJORHow SARMs May Complement Finasteride Or DutasterideAs DHT has a binding affinity higher than all SARMs, and significantly higher than all anti-androgens, if sufficient AR competition could not be achieved locally via a SARM or anti-androgen to stave off androgenic alopecia, then a 5-alpha reductase inhibitor could then be looked at as a potential adjunct treatment to use concurrently.By dropping systemic DHT levels via 5-alpha reductase inhibition, competing for AR becomes significantly easier for us as we have compounds at our disposal that are actually comparable to testosterone in binding affinity.The 500 Dalton Rule For The Skin Penetration Of Chemical Compounds And DrugsThe molecular weight of a compound must be under 500 Dalton to allow skin absorption [R].Larger molecules cannot pass the corneal layer.The Dalton is used as a unit of molar mass, especially in biochemistry.1 Da (dalton) = 1 g/mol.The Most Promising SARMs For Hair Loss PreventionTaking S4 (Andarine) as an example, you can see that the molecular weight is 441.4 g/mol [R].Because S4 has a molecular weight of 441.4 daltons, it can pass the corneal layer and work to some extent topically.I’m using S4 as an example simply because it seems to be the most hair safe SARM of all to date via oral administration, and is also the only SARM I have seen used topically so far.It is also the only SARM I’ve seen used orally in conjunction with exogenous estradiol for over a year straight so far with great success and no notable deleterious effects to liver enzymes or other health markers that are commonly impaired with high dosages of oral SARMs.With that being said, S4 isn’t without its potential issues itself.SARMs are still uncharted waters, but there are several that have been well tolerated in a clinical setting at dosages several times higher than what we would be using for hair loss prevention, or even for muscle growth in a bodybuilding context in a few token scenarios.While S4 has shown to be the most promising SARM in a hair loss prevention context to date, I am confident that other alternatives with improved binding affinities, high tissue selectivity, and high tolerability clinically in actual human subjects would likely result in similar positive outcomes if the dosing was nailed down.For example, LGD-4033 has a molecular weight of 338.25 daltons and has shown to be well tolerated in humans at dosages as high as 22 mg per day orally [R].It has also binds to the androgen receptor with an extremely high affinity (Ki of ~1 nM), which is superior to every other SARM tested on humans with comparable tissue selectivity.In addition, a preclinical rodent model showed that it has greater than 500-fold selectivity of muscle tissue to prostate when compared to testosterone.LGD-4033 Selectivity For Muscle To Prostate Compared To TestosteroneA greater than 500:1 anabolic to androgenic selectivity would make LGD-4033 the most tissue selective SARM to date.However, in practical application, LGD-4033 seems several times more androgenic than S4, although it is also several times more anabolic milligram for milligram.Some individuals even report hair loss with LGD-4033 use.Context is key here though, as the individuals reporting hair loss are using dosages 10x higher than the dosage being evaluated in humans clinically, and it is not clear whether this is telogen effluvium or actual androgenic alopecia progression even in these mega-dosing cases.This is what I mean by the dosing needs to be nailed down with these compounds, as haphazard overdosing could easily lead to unexpected androgenic activity, or induce telogen effluvium via a significant shift in endogenous hormones.There is no SARM that is completely devoid of androgenic activity, so dose response needs to be carefully assessed when experimentation is done with these compounds.Anabolism as a Systemic Effect of Topical SARMs for Hair LossOne of the limitations of anti-androgens is that when they go systemic they can induce anti-androgenic activity in other tissues.SARMs on the other hand bind to androgen receptors and induce tissue selective anabolic activity.So, the theory here is that we can potentially use a lower dose of a SARM topically than we would need with an anti-androgen, and achieve a substantial anti-androgenic effect via a much lower dosage, and even if it were to go systemic to some extent, then the worst that happens is we get some anabolic activity in muscle and bone.In theory, it sounds great, but SARMs will still suppress endogenous androgen production to some extent, lower SHBG, and potentially induce some hepatic stress when systemic.However, the degree to which this occurs should be much lower than what occurs with traditional anti-androgens.This is all theoretical at the end of the day, as SARMs may not even compete for AR activation in the scalp.However, anecdotally via oral administration it seems fairly obvious that they do in all tissues in the body, despite having “selective” action.If a topical anti-androgen works, then a topical SARM should work in a similar way.SARMs are essentially just chemically modified anti-androgens with better binding affinity and anabolic activity after all.Efficacy Profile Of Topical SARMs For Men Wanting To Retain MasculinityFor many men, hair is a huge part of their identity and plays a massive role in looking good.Unfortunately, we’ve been put in a position biologically where the more androgens in our body, the more expedited our hair loss progression will be, and all effective anabolic agents have some level of androgenicity.So, in a perfect world, we would be able to utilize SARMs (or something like SARMs) to selectively occupy androgen receptors in the scalp, and leave the rest of the body alone.Topical SARMs For Hair Loss Prevention: A Viable Long-term Strategy?While SARMs are still very new, there are already SARMs with comparable binding affinities to testosterone that have shown to have no virilizing effects in women at fairly high dosages orally.Topically, we may be able to achieve more localized action on androgen receptors and minimize the systemic impact in the body.I believe there are better ways to manage hair loss than blindly crushing androgen levels with primitive medications.SARMs may or may not be the answer, but they are certainly a step forward and could very likely be used effectively as a form of monotherapy in some users, or as an adjunct treatment alongside tried and true compounds that do a significant amount of the heavy lifting, and then let a SARM clean up the mess leftover.Are SARMs perfect?No, they aren’t.However, some of the SARMs currently developed may already have more therapeutic promise for some individuals than traditional anti-androgens used for hair loss prevention.At the very least, they are worth exploring more in this context, and I believe are potentially a more progressive way to go about handling excessive androgenic activity via AR activation in the scalp.In addition, injectable SARMs are a new area I’m researching that may also have therapeutic promise as well.How To Create A Topical SARMThe ideal scenario would be that we mix a SARM into a topical solution that has shown to not only be very tissue selective with a high binding affinity, but has also shown to be well-tolerated in humans in a clinical setting with no deleterious outcomes, and then apply that solution topically to bind locally to androgen receptors and compete with testosterone and DHT for AR activation.Standard vehicles (the carrier solution you mix the compound in for topical application) should work similarly to anti-androgens.My guess is that a 70% ethanol/30% propylene glycol vehicle would suffice.A PEG 400 mixture may be a useful alternative vehicle for those with intolerance to propylene glycol, or those with vehicle-dependent contact allergy to SARMs in either propylene or hexylene glycol [R].Adding a bit of DMSO or daily microneedling with a short length pretreatment may need to be incorporated for absorption for those with less permeable skin.What concentration the solution should be remains up in the air and will need to be determined via experimentation.Following the dosage outlines used in a therapeutic setting, we can get a well-tolerated starting point.For example, with LGD-4033, orally it has a tissue selective anabolic effect at dosages as low as 0.1 mg per day, and has shown to be well-tolerated as high as 22 mg per day.The most notable clinical trial on LGD-4033 utilized 0.5 mg, 1 mg and 2 mg orally for 12 weeks.LGD-4033 exhibited encouraging safety and tolerability, and there were no drug-related serious adverse events in the study [R].A good starting point would be 0.5 mg LGD-4033 per day topically, with the dosage titrated up accordingly based on dose-response.The only SARM I’ve seen used topically to date is S4.As S4 does not have any human data, we had to design the protocol based around anecdotal findings and extrapolated clinical data on rodent models.Anecdotally, orally administered S4 does not induce night vision side effects until around 30-50 mg per day.A topically administered dosage of 25 mg per day produced a very quick reduction in sebum in the scalp, which is a very obvious marker of reduced androgenic activity.Scalp itch was also severely decreased, with no notable side effects.Notably, the individual who I oversaw who did this experiment gets horrible side effects from every single hair loss prevention compound he has tried.He’s one of the unfortunate ones who gets brutal 5-alpha reductase inhibitor side effects, systemic anti-androgen side effects with topical anti-androgen use, and even severely impaired sleep with PGD2 inhibitors.The fact that he had no issues with topical S4 was very promising, and piqued my interest in the area even more (which is partially what has led me to my current injectable SARMs experiment I am conducting on myself).Does that mean this is a viable long-term strategy?That remains to be seen with further experimentation.To be clear, this is still a theoretical approach to topical hair loss prevention, and is geared mostly towards individuals who have experienced negative side effects with 5-alpha reductase inhibitors, RU58841 and CB-03-01.Where To Buy SARMsMost companies do not third party test their products, nor do they have any satisfactory level of quality control whatsoever.I strongly advise that before you buy SARMs from a company online you thoroughly evaluate their track record, their third party test results, and how they are marketing their products in general.These Are My Current Trusted/Go To Companies For Third Party Tested 99%+ Pure SARMs:Science.bio – 10% off coupon code “DC10”Chemyo – 10% off coupon code “DC10”Amino Asylum – 20% off coupon code “DC20”Swiss Chems – 25% off coupon code “DC25”Disclaimer: The information included in this article is intended for entertainment and informational purposes only. It is not intended nor implied to be a substitute for professional medical advice. Prior to buying anything, check that it is compliant where you live with your current government laws.Related

There’s a misconception that Finasteride is a reliable source of remedy for hair loss prevention caused by the intake of all anabolic steroids.For anyone who has reviewed the downstream mechanisms of Finasteride in the body, it is clear that this is not true.Below are the details to a realistic set of expectations from Finasteride use with anabolic steroids.[embedded content]Table of ContentsNot All Steroids Convert to DHT via 5-Alpha ReductaseAn assumption that must be ruled out is the idea that dihydrotestosterone (DHT) will always be the by-product of metabolic reactions between 5-alpha reductase and an anabolic steroid.5-alpha reductase is an enzyme involved in steroid metabolism that can create androgenic metabolites (e.g. DHT) via a process called “5-alpha reduction”.While several studies indeed support the idea that DHT is an influencer for hair-loss and that anabolic steroids all have a certain tendency to interact with 5-alpha reductase, most of the steroids used for bodybuilding and powerlifting are not potent substrates for 5-alpha reductase, if they interact at all.Testosterone is the only anabolic steroid that is converted to DHT via 5-alpha reductase, which is contrary to the common misconception that all other anabolic steroids would also be converted to DHT.Other steroids that are substrates for 5-alpha reductase are converted to unique metabolites with their own individual anabolic and androgenic potency.For example, Boldenone (Equipoise) can be converted to dihydroboldenone (DHB) via 5-alpha reductase.Nandrolone can be converted to dihydronandrolone (DHN) via 5-alpha reductase.The two metabolites DHB and DHN each have their own unique anabolic and androgenic potency and will not be equal to one another, nor will they be equal to DHT.Testosterone vs. Other Anabolic Steroids as a Catalyst for Hair LossExcessive intake of testosterone can definitely result in an increased susceptibility to hair loss due to its interaction with 5-alpha reductase to produce DHT, as well as via its inherent anabolic activity, albeit to a much lesser extent.Meanwhile, certain synthetic anabolic steroids such as Primobolanare designed to maximize the anabolic activity in the body with a lower incidence of androgenic activity and do not interact with 5-alpha reductase at all. However, just because a steroid does not interact with 5-alpha reductase that does not mean that the parent hormone is hair safe whatsoever.There are several other steroids that do not interact with 5-alpha reductase that will still cause hair loss.The overarching concept that needs to be remembered is that all steroids have their own individual level of anabolism and androgenicity in tissues.Regardless if a steroid is a 5-alpha reduced metabolite, or a parent hormone, they are all still steroids at the end of the day with their own anabolic and androgenic impact on affected tissues in the body, and they need to all be accounted for.Anabolic Steroid Interaction With 5-Alpha ReductaseFinasteride is essentially a downstream androgen synthesis inhibitor.This particular medication reduces the formation of the potent androgen, dihydrotestosterone (DHT), from its precursor testosterone by successfully inhibiting the 5-alpha reductase enzyme.Since DHT is several times more androgenic than testosterone, this would significantly decrease the amount of androgenic influence on the body.An important aspect to take into consideration is that the parent hormones themselves are inherently androgenic to a significant extent.In fact, with some steroids, the metabolites could be far less androgenic than the parent hormone, in which case 5-alpha reduction could actually be more hair loss sparing.[embedded content]Nandrolone is an example of this, where the parent hormone (nandrolone) is more androgenic than its metabolite produced via 5-alpha reduction (DHN); subsequently making concurrent Finasteride use an accelerant of androgenic alopecia.Finasteride Only Prevents DHT Derived Hair LossTo sum up, Finasteride may meaningfully prevent hair loss only if the cause is due to excess DHT.This is because DHT is more several times more androgenic than testosterone.DHT exhibits such poor anabolic tissue selectivity that it is one of the few steroids that actually features an androgenic rating several times higher than its anabolic rating.In short, DHT sucks at building muscle.In a study conducted to determine whether the intake of Dutasteride would affect muscle mass accrual, those treated with the medication had similar results to the untreated control group; meaning that the decreased DHT level had no significant anabolic impact on muscle growth.Even by nearly wiping out the participants’ DHT levels with Dutasteride, they did not experience hindered muscle growth at all in response to graded testosterone doses [R].In fact, an argument can be made that inhibiting 5-alpha reductase can mediate supraphysiological muscle growth due to a higher ratio of testosterone to DHT.This is apparent in pseudohermaphrodites who are inherently 5-alpha reductase-deficient due to genetic mutations [R].In this particular study involving brothers with different DHT levels, the male with 5-alpha reductase deficiency experienced reduced sexual development throughout puberty, but also gained more muscle mass than his brother.In the image below, the man on the left has a 5-alpha reductase deficiency, and his brother on the right doesn’t have a deficiency.The man on the left has a higher testosterone level, is more muscular, and has less androgenic alopecia than his brother on the right who has normal DHT levels.The Steroids Finasteride Or Dutasteride Can Protect Your Hair FromFinasteride and Dutasteride do not occupy or inhibit androgen receptors, but rather they inhibit the 5-alpha reductase enzyme primarily responsible for converting testosterone to DHT.These medications are extremely effective at reducing DHT levels, hence why natural athletes and those on mild doses of exogenous testosterone typically experience the attenuation of hair loss progression with it, or at least some degree of slow down (dependent on the individual’s androgen receptor density, sensitivity, residual DHT levels, free testosterone levels, and a myriad of other less relevant factors).Those who blast Trenbolone, or any other anabolic steroid, will not be protected from the androgenic activity of those hormones on the scalp.It is essential to thoroughly understand the mechanism of action of everything going into your body prior to haphazardly popping pills in attempts to blindly remedy a side effect like hair loss, as you may be wasting your time, or even potentially make the situation worse.Related

It’s theorized in the bodybuilding community that the reason Flex Wheeler and other top Olympia caliber bodybuilders are able to build such incredible physiques is due to Myostatin deficiency.Other popular theories circulate around that include ideas as vastly different as androgen receptor sensitivity is higher in top bodybuilders, to the complete opposite side of the spectrum where some believe that training past a certain pain threshold is what separates champions from the rest and that genetics are just a small factor in determining bodybuilding success.In this article I delve into Myostatin gene mutations, claims about top Mr. Olympia bodybuilders’ DNA, and outline what kind of potential impact Myostatin has shown to have in the clinical data.In addition, I take a deep dive into the actual study conducted on Flex Wheeler and a handful of other Mr. Olympia contenders and show what was revealed about their DNA, as well as how it compared to average individuals.Table of ContentsMyostatin Gene (MSTN) and Its Role in Myostatin ProductionBefore delving into a real-world example of a purported Myostatin deficiency in humans (Flex Wheeler), I’m going to get into the gene a bit itself.The MSTN gene is a gene that makes instructions for producing the protein myostatin.Myostatin regulates skeletal muscle growth by restraining it when necessary.In turn, it prevents the body from gaining too much muscle.Current research that surrounds myostatin is based around its treatment for musculoskeletal degenerative diseases.Coincidentally, animals that have mutations in the encoding gene MSTN show greater muscle mass, strength, and in some circumstances reduced body fat as well.Examples of Myostatin deficiencies are found in lab based rodent models, as well as in the farming industry with myostatin deficient cattle.Myostatin Knockout MiceMice that lack the gene that creates myostatin have approximately twice as much muscle mass as normal mice [R].Myostatin inhibitors have been proposed by many to be the most promising new area of science in a bodybuilding context, as well as potentially better alternative treatment for muscle wasting diseases.Belgian Blue Double-Muscled CattleThe Belgian Blue has a myostatin gene mutation, consequently preventing its feedback loop of muscle growth inhibition from working correctly.This mutation interferes with fat deposition and can lead to accelerated lean muscle growth.The acceleration of muscle growth in Belgian Blues is due primarily to physiological changes in the animal’s muscle cells (fibers) from hypertrophy to a hyperplasia mode of growth.This growth occurs in the fetus and results in a calf being born with two times the number of muscle fibers as a calf without a myostatin gene mutation [R].Myostatin Elevates In Response To AndrogensWhile there are likely other counterregulatory mechanisms in the body that inhibit excessive muscle growth, the main factor appears to be myostatin elevation.Myostatin increases to prevent you from gaining unhealthy amounts of muscle.In the following study, the effects of exogenous testosterone and trenbolone on myostatin levels was evaluated [R].This study showed that after 29 days of administration of either testosterone or trenbolone, myostatin protein levels were 197% higher in the castrated and testosterone group, and 209% higher in the castrated and trenbolone group when compared to the placebo.There’s a reason why this mechanism is in place in our bodies and we can’t grow linearly.Too much of anything is not going to be good, and when you try to push your body to a place that isn’t healthy, homeostatic mechanisms in the body will try to stop you.The human body is a big balancing act.More Androgens = More Myostatin = More Muscle Growth InhibitionAs previously outlined, myostatin is a growth inhibitor that elevates in the presence of androgens.Based on the current research it appears that the higher your dose of exogenous anabolics, the greater muscle growth potential you have, and consequently the higher your myostatin will elevate in parallel to inhibit absurd rates of muscle growth.In a study evaluating the effect graded doses of testosterone have on myostatin levels in young and older men, myostatin levels were significantly higher on day 56 than baseline in both groups [R].The myostatin hypothesis isn’t air tight and has some holes in the data contradicting its muscle growth inhibiting effects.However, based on what we know to date, the research suggests that its more than likely the main regulatory mechanism involved in muscle growth response relative to androgen receptor activation.Myostatin is well known to negatively regulate muscle mass in mice, cattle, dogs and humans [R].Myostatin Is Elevated In HIV Positive IndividualsMyostatin is detectable in human skeletal muscle, and its expression is increased in the muscles of HIV-infected men with muscle wasting compared to that in normal men [R].Does this mean that the muscle wasting that occurs with disease is caused in part by myostatin elevation?Maybe, and the relationship between the two is definitely notable.Studies Measuring How Much Myostatin Gene Mutations Can Affect Bodybuilding ProgressA small study was conducted to discover if the mutations in the SNP rs1805086 have any impact on the male bodybuilding population from a muscle hypertrophy and muscle performance standpoint [R].The secondary aim was to speculate if rare mutations are more prevalent in those who decide to choose a sport such as bodybuilding, as research indicates that mutations in MSTN can illicit larger muscle mass gains and a reduction in body fat.The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A >G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes and is listed on SNPedia as the top risk genotype for causing myostatin-related muscle hypertrophy [R, R].17% of the subject group had one mutation (AG), 83% had the common outcome (AA) and 0% (0) had two mutations (GG).Those with the AG genotype had an average arm circumference of 46.37 cm compared with AA which had an average of 42.02 cm.Those with the AG genotype had an average pull-up max score of 21 compared with AA with an average of 12.Those with the AG genotype had an average push-up max of 61 compared with AA with an average of 40.The study clearly shows that those with a mutation are rare, however the mutation does appear to give the subject a performance and size advantage over those with the common outcome.Another study had similar findings when evaluating A55T and K153R polymorphisms [R].Our results indicated that individuals with AT + TT genotype of the A55T polymorphism showed a significant increase in the thickness of biceps (0.292 ± 0.210 cm, P = 0.03), but not quadriceps (0.254 ± 0.198 cm, P = 0.07), compared to carriers of AA genotype.For the K153R polymorphism, the increases in the thicknesses of both biceps (0.300 ± 0.131 cm) and quadriceps (0.421 ± 0.281 cm) were significantly higher among individuals with KR than those with KK genotypes (P < 0.01 for both muscles).The results obtained therefore suggested a possible association between the two polymorphisms and the strength training-induced muscle hypertrophy among men of Han Chinese ethnicity.The K153R polymorphism is the same Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A >G replacement) of the myostatin (MSTN) gene evaluated in the first study mentioned.SNPs Found To Influence Myostatin-Related Muscle HypertrophyAccording to SNPedia, these 3 SNPs definitely relate to myostatin-related muscle hypertrophy:The rs1805086 SNP in particular is the one most commonly looked at in relation to bodybuilding outcomes.It is often referred to during discussions of the “bodybuilder gene”.The rs1805086 SNP genotype AA is seen as the commonly occurring one, with the risk alleles being the rs1805086 GG genotype.The disease literally listed as a potential outcome of having this risk genotype is myostatin-related muscle hypertrophy.Just having one G allele is rare to begin with, and being homozygous for it is very rare.In my first video, I was basing my conclusion of Flex Wheeler’s genetic significance solely off the extrapolation of Victor Conte’s broad statement in his letter.[embedded content]I assumed that Flex probably had the rarest GG genotype for the rs1805086 SNP.However, after digging into the study conducted on Flex Wheeler itself, we are led to what is likely a much different conclusion, and is what I will delve into next.Flex Wheeler Myostatin DeficiencySupposedly, Flex Wheeler was a participant in a study conducted in collaboration with the department of human genetics at the university of Pittsburgh involving 62 men.During this study, Flex was purportedly found to have a very rare myostatin mutation at the exon 2 position on the gene.In theory, this supposed gene mutation prevented his body from producing normal amounts of myostatin, consequently resulting in a much larger number of muscle fibers than the average male.Animals and humans with inhibited myostatin levels have consistently shown to have much greater levels of musculature relative to their non-inhibited counterparts, and based on this it isn’t crazy to assume that genetic freaks in bodybuilding developed their physiques as a result of a similar gene mutation.In theory, someone with low myostatin levels could continue to progress at rates that would be impossible for someone with normal myostatin levels.The end result of chronically low myostatin levels could potentially be substantially greater levels of muscle gain from the exact same diet, training and drugs.Victor Conte’s Letter About Flex WheelerVictor Conte is one of the individuals associated with the myostatin mutation study conducted on Flex Wheeler and an assortment of other IFBB pro bodybuilders.99% of those in the bodybuilding community who discuss Flex’s myostatin deficiency are referencing a letter written in October, 1998 by Victor Conte.Whether this letter is legitimate and unaltered is unclear, but for what it is worth, we will assume it is legit as it is what has circulated around our community for years.October 1, 1998Re: Flex WheelerTo whom it may concern:I am writing this letter per the request of Flex Wheeler.I would first like to briefly provide you with some background information regarding BALCO Laboratories. BALCO has been working with elite Olympic and professional athletes for over fifteen years. BALCO has provided testing and consultation for over 250 NFL players including the entire 1998 Super Bowl Champion Denver Broncos team and the entire Miami Dolphins team. BALCO works with professional athletes in many sports including tennis (Michael Chang, Jim Courier, etc.), hockey, bodybuilding (10 of the 16 1998 Mr. Olympia contestants), track and field, soccer and basketball (Seattle SuperSonics).BALCO Laboratories has been testing and monitoring Flex on a routine basis during the last year. We have performed tests including blood chemistry (SMAC), complete blood count (CBC), PSA, anabolic hormone levels, genotyping as well as comprehensive testing for nutritional elements. Flex’s test results have been compared to twenty-four other professional bodybuilders and overall he has one of the healthiest profiles. Basically, Flex is in excellent health and has demonstrated the discipline necessary to maintain a peak level of conditioning.Flex was a participant in a study we recently conducted in collaboration with the Department of Human Genetics at the University of Pittsburgh involving 62 men who made unusually large gains in muscle mass in response to strength training (extreme responders). Flex was one of only nine extreme responders that had the very rare “myostatin mutation.” Myostatin is the gene that “limits muscle growth.” Specifically, Flex had the rarest form of myostatin mutation at the “exon 2” position on the gene. This simply means Flex has a much larger number of muscle fibers compared to the other subjects or the normal population. We believe that these are the very first myostatin mutation findings in humans and the results of this landmark study have already been submitted for publication. Flex was also found to have a very unusual type of the IGF-1 gene. In fact, Flex was the only participant in the study that did not have a “match.” All of the other extreme responders had at least three other subjects with a matching IGF-1 gene. Based upon Flex’s very unique genetic profile, we plan to expeditiously publish a scientific paper that reveals his complete genotype in specific detail. The publication of his remarkable genetic data should generate an enormous amount of media exposure.Hope this information will be helpful and please call if I can be of assistance.Sincerely,/s/ Victor ConteVictor ContePresidentBALCO Laboratories, Inc.The Myostatin Mutation Study Conducted On Flex Wheeler And Other IFBB ProsThis study is commonly referenced but I have yet to see someone actually dig it up and cross reference the data in it with the statements made in Victor Conte’s letter.I did some digging and found it.The study is called “frequent sequence variation in the human myostatin (GDF8) gene as a marker for analysis of muscle-related phenotypes” [R].Based on what Victor stated in his letter, there were nine extreme responders with a very rare myostatin mutation.Supposedly Flex Wheeler had the rarest mutation of all at the exon 2 position on the gene, making him unique from all other individuals in the study.[embedded content]Subjects In The StudySequencing of selected regions of the myostatin gene and genotyping of common variants were carried out in a comparison sample of 96 randomly selected Caucasian and 96 African American subjects from the general population.An additional 72 individuals were screened for a common exon 2 variant.One hundred fifty-three subjects, including 127 men (32 African American, 91 Caucasian, and 4 Asian) and 26 women (9 African American, 16 Caucasian, and 1 Asian), were categorized by the magnitude of increases in muscle mass they experienced from strength training.The subjects consisted of:18 world-class bodybuilders (ranked in the top 100 worldwide)25 competitive bodybuilders not ranked in the top 1007 elite power lifters9 university football players55 previously untrained subjects who had their quadricep muscle volume measured by magnetic resonance imaging before and after 9 weeks of heavy resistance strength training of the knee extensors61 nonathletes, who were questioned about their ability to increase their muscle mass in response to intense and prolonged strength training5 of the 18 world-class bodybuilders were Mr. Olympia contenders ranked in the top 10 worldwide. [embedded content]A rating of 5 was given to those who were world-class bodybuilders and to those who increased their quadriceps muscle mass by more than 400 cm³ after only 9 weeks of strength training, whereas a rating of 0 was given to those who experienced no noticeable increase in muscle mass after vigorous strength training for at least 6 months.Eighteen subjects received a rating of 5, and 13 subjects received a rating of 0.The ratings of the remaining subjects fell somewhere between these two extremes.62 subjects who were rated as either 4 or 5 were classified as extreme responders, and were compared to 48 subjects who were rated as either 0 or 1 and were classified as nonresponders.Subjects were also grouped and compared by race.Information on muscle mass changes with strength training from the remaining subjects was obtained through either estimates of fat-free mass assessed by dual-energy X-ray absorptiometry or hydrodensitometry or in the case of competitive bodybuilders, power lifters, football players, and nonathletes, through questionnaire data on prior success in bodybuilding competition and/or reported changes in muscle mass with strength training.Study ResultsWithout boring you with the less relevant details in the study, the most notable part is the conclusion.The lack of a significant relationship between myostatin genotypes and overall muscle mass response to strength training suggests that response is not significantly influenced by variation at the myostatin locus.However, it is interesting to note that three of the African American nonresponders were homozygous for the less common (Arg) allele at the exon 2 K153R site, while none of the responders were homozygous for this allele.Three of the five mutations causing the double muscle phenotype in cattle occur in exon 2 and are recessive, but two are chain termination mutations and one is a deletion, expected to produce a nonfunctional myostatin protein.Whether variation in the myostatin gene influences muscle phenotypes other than the muscle mass increase in response to strength training requires further exploration.The less common Arg allele that is being referred to in the study conclusion is the mutation that you would expect Flex Wheeler to have.But, it doesn’t appear that he has it.Sandwiched in the middle of the study is a mention of what may be highlighting the true root of Flex’s genetic superiority.Among the six nucleotide changes, two, P198A and the intron 2 A/G, were observed in a single individual and two, I225T and E164K, were observed in two individuals, always heterozygous with the wildtype allele.The remaining two were present in the general population as common polymorphisms.The (A55T) and (K153R) variants are common in both ethnic groups, with the less frequent allele having a three to four times higher frequency in African Americans.These variable sites have the potential to alter the function of the myostatin gene product and could alter nutrient partitioning in individuals heterozygous or homozygous for the variant allele.What we can presume Flex Wheeler has is two nucleotide changes, P198A and the intron 2 A/G.That is the only note in the entire publication that distinguishes one individual in the study from the rest.What we can presume to be the nucleotide changes Flex Wheeler has aren’t even mentioned on SNPedia’s list of related risk genotypes.The only vague reference we have to it is in a study that examined the association between the MSTN exonic variants and ‘explosive’ leg power in 214 male university students [R].And in that study the only thing mentioned is that no subjects in the study had the MSTN exonic variant P198A.It appears that despite the uncommon (Arg) allele at the exon 2 K153R site being the main focus of most Myostatin papers and being honed in on as the root of the “bodybuilder gene”, it does not seem to have as significant of an impact on muscle growth response to training as many thought at the end of the day.The lack of a significant relationship between myostatin genotypes and overall muscle mass is very notable as this study included 5 Mr. Olympia caliber bodybuilders, and several other top tier IFBB pros.The most interesting thing to note is that three of the African American nonresponders were homozygous for the less common (Arg) allele at the exon 2 K153R site, while none of the responders were homozygous for this allele.Of the identified GDF8 variations in humans, the Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A >G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes [R].None of the extreme responder bodybuilders were homozygous for this allele though.I had mentioned in the first video that having the AG genotype in general is rare.It was found to have a significant impact on muscle size and muscle strength in the study I outlined earlier in the article.Logically, you would assume that the GG genotype (which is even more uncommon), would result in a lack of myostatin and some insane level of muscle growth.That doesn’t seem to be the case though based on this study.3 of the subjects who had a poor response to training and subpar muscle growth (nonresponders) were the ones who had this rare genotype.Only three individuals had extremely rare nucleotide changes.This includes who I assume to be Flex who has two nucleotide changes, P198A and the intron 2 A/G, and two other individuals having I225T and E164K nucleotide changes, all of which were heterozygous with the wildtype allele.That leaves 2 top tier Mr. Olympia caliber bodybuilders, several other world class IFBB pro bodybuilders, and a lot of other elite athletes, with MSTN genotypes that have shown to have minimal impact on muscle growth response to training in this study.The two other nucleotide changes causing the double muscle phenotype in cattle are the A55T and K153R variants and are present in the general population as common polymorphisms.These variable sites have shown potential to alter the function of the myostatin gene product and could alter nutrient partitioning in individuals heterozygous or homozygous for the variant allele.However, the data in this study shows that there is not a significant relationship between myostatin genotypes and overall muscle mass response to strength training.Inconsistencies In The Clinical Data And Victor Conte LetterI don’t know where the statements in the letter Victor wrote are coming from.He claims that Flex Wheeler had the rarest form of myostatin mutation at the exon 2 position on the gene.But when we look at the study itself, it says 3 of the non-responders were homozygous.None of the responders were homozygous.Flex Wheeler would have undoubtedly been categorized as an extreme responder, and yet, he was not one of the individuals with the GDF8 variation in humans we would expect to see in a myostatin deficient individual.Based on this, we can presume he is the individual mentioned in the study with two nucleotide changes, P198A and the intron 2 A/G.Victor also mentioned how “nine extreme responders had the very rare myostatin mutation.”We can see in the data that only three individuals had uncommon nucleotide changes, not nine, and the rest of the subjects had common polymorphisms present in the general population.In addition, of the mutations mentioned, even if more of the top caliber bodybuilders had notable mutations, the study conclusion still states that there is not a significant relationship between myostatin genotypes and overall muscle mass response to strength training.Victor also stated in his letter that Flex is one of the healthiest of his professional bodybuilders he’s been monitoring, and that Flex is in excellent health.We have performed tests including blood chemistry (SMAC), complete blood count (CBC), PSA, anabolic hormone levels, genotyping as well as comprehensive testing for nutritional elements.Flex’s test results have been compared to twenty-four other professional bodybuilders and overall he has one of the healthiest profiles.Basically, Flex is in excellent health and has demonstrated the discipline necessary to maintain a peak level of conditioning.This was written on October 1, 1998.If you know the history of Flex Wheeler, you’ll know that he ended up having to stop competing after discovering in 1999 that he had focal segmental glomerulosclerosis (a form of kidney disease), and then retired shortly thereafter.I don’t know how something that massive could be overlooked to that extent.It makes me question the legitimacy of this letter in the first place.If Flex was truly on the brink of kidney failure, I don’t see how it was determined that he was one of the healthiest bodybuilders being supervised by Victor, and how this extensive testing didn’t pick this up.The first thing that comes to my mind is curiosity around whether or not there was some sort of money-making endeavor associated with this.The supplement industry was crazy in the 90’s.Steroids were sold legally over the counter, and you could make ridiculous false claims about pretty much whatever you want and then sell products based on that.The false claims are still around today, but now we have the resources at our fingertips to actually see through the garbage being marketed to us, whereas in the 90’s nobody knew better and a myostatin inhibiting supplement that can make you as jacked as Flex Wheeler likely would have sold like crazy.Maybe this guess is way off of what the real intention was, but I don’t see what could have been the motivation behind this letter, or what it was seeking to accomplish.It is entirely possible that they were thinking of teaming up to create some sort of myostatin inhibitor supplement that would be based on Flex’s unique genotype.ConclusionI don’t know if the further publication that Victor mentioned in the letter ever came to surface.Based upon Flex’s very unique genetic profile, we plan to expeditiously publish a scientific paper that reveals his complete genotype in specific detail.The publication of his remarkable genetic data should generate an enormous amount of media exposure.I’m assuming that this was probably put on the back burner after Flex had his health issues in 1999.I don’t know what the goal of this letter was, and there are several inconsistencies between it and the actual study that would need further clarification to make any conclusive statements.Who was this letter addressed to and why was Flex Wheeler requesting this letter be written in the first place?Aside from the mystery of this letter that greatly interests me, it seems like we can at least conclude based on the study findings that most myostatin gene mutations do not appear to be the differentiating factor between top Mr. Olympia caliber extreme responders and the average joe.Related