Injectable SARMS vs Oral SARMS

/Injectable SARMS vs Oral SARMS

Injectable SARMS vs Oral SARMS

Injectable SARMS vs Oral SARMS

Selective Androgen Receptor Modulators, or SARM’s, is in an area of performance enhancers that are still misunderstood and filled with misconceptions due to bad information that is regurgitated over and over again. Much of this bad information is due to people reading abstract research articles that are available online and misinterpret the findings due to the individual’s lack of understanding of the subject, general ignorance in science, and without adequate knowledge on how to analyze the research information.

For example, one study using 0,1,2, and 3mg of LGD-4033 on geriatric patients with muscle atrophy due to disease or prior conditions. The conclusions found that each group taking more than the placebo dose increased lean body mass composition and lost body fat. These patients also had nearly 0 suppression and side effects. Sounds incredible, right?

Well, for someone without a general understanding of how to dissect and interpret the findings would come to that conclusion. However, these patients all had extremely low testosterone levels, their health was deteriorating, they had less muscle than average, and it was only getting worse. This study only showed what SARMS are effective at this dose for those people that fit this profile in the experiment. None of these results are applicable or replicable in any athlete nor healthy adult male.

Take a 16-year-old boy going through puberty and give him the 3mg of LGD. The child would have either 1. Suppression and interruption of his endogenous production of testosterone, and at the most important time in a male’s life. Little to no benefit in muscle growth and performance by adding it because of the testosterone shutdown having more detrimental effects that overpower the benefit of the dose of the SARM given (he would still see improvement from training and eating, just less than he would naturally).

There are countless articles online with findings that can be interpreted differently by the individual reading it. Even more confusing are the variables in the methods and procedures that are not understood by the person reading it. This one key point alone can be the difference in reading and interpreting as, “that “x” drug cured muscle atrophy and gives 3lbs of muscle a month even when sedentary, vs reading, “That “x” drug reversed muscle atrophy in patients with “y” disease-causing muscle dystrophy, due to the lack of testosterone production. Without the understanding of the vocabulary used in the field or general scientists, how can someone even interpret the findings? Hopefully, this extended introduction has made you more aware when reading into this topic (including this article) and more open to questioning rather than seeing only white and black.

So from the research that has been done already, and the current research we have been doing, I will help explain how these powerful synthetic steroids function, future potential, the real secrets behind them, and how to use this knowledge to properly use, combine, and manipulate them the most effective way possible. But before we get to the secrets, we need to understand.

With the available research we have on SARMS, we know that they do not undergo aromatization or 5-alpha reduction and that this may also be the reason behind their lack of effects on the prostate and/or side effects. Preclinical studies of the first generation SARMs in animal models have shown anabolic effects on skeletal muscle mass, bone mass and density and varying degrees of tissue selectivity without affecting the prostate. But its known and proved in Early phase I and II trials that ALSO reported modest increments in fat-free mass and significant reductions in high-density lipoprotein (HDL), cholesterol, and SHBG. This doesn’t mean that the hormones that these enzymes are metabolizing aren’t affected by the SARM, resulting in side effects identical to oral steroid usage.

Other than SARMS being much stronger mg/mg with fewer side effects, and the potential for new growth that steroids cannot offer. Why would we take experimental research drugs if we get the same or similar side effects as steroids when we already know how steroids work generally speaking? Well, we wouldn’t, unless it was offering more benefit or fewer side effects for one, and it would be hard to argue for it if the reasoning if it was solely based on results with no side effects, or vice versa.

However, let me explain how the literature and real-world results conflict with each other, just like they did when the first anabolic books came out about steroids. The literature showed one effect and promise, and the athletes all taking it reported drastically different effects. And until this day you can verify the side effects of stanozolol listed via any medical site, and compare it yourself from experience of clients. If I said Winstrol-injection produces excessive edema and swelling due to water retention of the hormone, you would stop reading now. However, this is what a side effect of stanozolol is listed. The SARMS studies are being used in patients who are either suffering from some type of muscle wasting disease or are children, women, elderly men and women who are declining in muscle mass due to lack of hormones/age. The dosing needed for these patients varies between 1-5mg/day.

When athletes consume SARMS for a performance-enhancing benefit, they are taking doses higher than what is being used in the clinical trials, sometimes much higher 30mg, and stacked with multiples, just to see muscle increase or some type of performance-enhancing effect at all. But along with this newly obtained muscle comes with it some potential side effects that do not show up in the patients in these trials.

For the most part, the side effects that an individual can actually feel or see change is the physical changes of acne or shutdown of their natural testosterone, and that is about all. However, go into your blood work and check your hormones and full metabolic panel and you will see a cascade of negative effects occurring with increases in the dosing taken orally. Now that being said, it is true that the side effects are typically mild in comparison to steroids, however, the dosing on the SARMS in the studies like 5mg is 1/10th dosing of steroids (mg to mg). For example, people take roughly between 100-150mg of Anavar or Winstrol per day, would destroy your liver and I guarantee you that 15-20mg of YK-11 (minus S-4 or maybe Ostarine) could give you dramatically more results without any liver toxicity.

Now you can start to see the dilemma we are having here when we now have to compare a substance claiming its side effect-free, or minimal, but has the performance increases of steroids. But the dosing required for this increases the side effects like steroids would when taken in higher amounts, just on a lesser scale. It sounds like another steroid but with higher anabolic potential and carrying less androgenic effects, much like Primobolan. That all these are, more improved versions of anabolic steroids, just increasing the anabolic activity and reducing the androgenic portion of the steroid. So why are the results not supporting the chemical properties that the drug would show in literature with its side effects, Or even in the real-world application?

Well, its very simple, it’s in its delivery form, it’s a pill… How many times have you heard of orals being methylated in order to absorb efficiently in the body because the active drug is greatly deteriorated or destroyed by either your stomach acids or the first pass of metabolization by your liver? But the side effects are more extreme or apparent with the oral, shortening the length of time you can take it. Now you can see the correlation between the two and make sense of the rest. With this basic understanding, the rest will be easy to read and understand as I explain this step by step, in a simple way, the reasoning for the side effects, obstruction in possible performance, and how we solved this problem.

List of Side Effects Oral Steroids and SARMS

List of Side effects Oral Steroids and SARMS can and will have a dose dependency. (Avoided or Drastically Reduced by injection method vs taken orally)

  • Hepatic – Cholestatic jaundice with, rarely, hepatic necrosis and death. Hepatocellular neoplasms and peliosis hepatis have been reported in association with long-term androgenic-anabolic steroid therapy. Reversible changes in liver function tests also occur including increased bromsulphalein (BSP) retention and increases in serum bilirubin, glutamic oxaloacetic transaminase (SGOT), and alkaline phosphatase.
  • Genitourinary System – In men, Prepubertal: Phallic enlargement and increased frequency of erections.
  • Postpubertal – Inhibition of testicular function, testicular atrophy and oligospermia impotence, chronic priapism, epididymitis, and bladder irritability.
  • In women – In women: Clitoral enlargement, menstrual irregularities.
  • Both sexes – In both sexes: Increased or decreased libido.
  • CNS – Habituation, excitation, insomnia, depression.
  • Gastrointestinal – Nausea, vomiting, Bloating diarrhea, Acid reflux.
  • Hematologic – Bleeding in patients on anticoagulants.
  • Breast – Gynecomastia.
  • Larynx – Deepening of the voice in women.
  • Hair – Hirsutism and male pattern baldness in women.
  • Skin – Acne (especially in women and prepubertal boys).
  • Skeletal – Premature closure of epiphyses in children.
  • Fluid and Electrolytes – Edema, retention of serum electrolytes (sodium, chloride, potassium, phosphate, calcium).
  • Kidney – Stressed or damaged kidneys due to electrolyte imbalances and increased creatinine and protein metabolization.
  • Metabolic/endocrine – Decreased glucose tolerance, increased serum levels of low-density lipoproteins and decreased levels of high-density lipoproteins (see PRECAUTIONS, Laboratory Tests), increased creatine and creatinine excretion, increased serum levels of creatinine phosphokinase (CPK). (Some virilizing changes in women are irreversible even after prompt discontinuance of therapy and are not prevented by concomitant use of estrogens.)

Dose Related Side effects of an Oral given SARM

Let’s say 10mg causes “x” amount of side effects when administered orally due to the enzyme metabolism process by your body, the processes after this while transporting the SARMS and binding to receptors that activate the counterbalancing hormone changes causing a cascade of imbalances in many other hormones in response. And finally, the purging/removal of the drug. Then It would be very apparent that 50mg would further increase these side effects or create more side effects than were noted before, correct? Oral administered medication is even more sensitive to side effects due to the stomach and liver’s role in altering or filtering of these before it reaches your system. By this time, it’s already too late. You may only get 10% of a drug because of its break down or metabolization during the liver pass, and stomach acid.

With this being clear now, the first question I think of is, why is only 10% absorbing? And what % of SARMS make it through? Well, the numbers vary and are given in the book but for the sake of ease let’s use between SR-9009 (2%) to GW(63%), or second wisest (s-23 being the highest in the ’90s) in bioavailability, and the rest are hidden or not found. This sounds like a joke that a drug would have such low absorption, yet still, be given this way, it was when oral steroids were being experimented on, which lead them to methylation to make it effective enough to take orally, but also toxic. So, if 10mg of a substance is strong enough to give results of TRT with little to no side effects (disregarding women), But only 2-7mg is absorbing, then we have the strongest anabolic compounds known to man here. The next question that comes to mind is if the effects we get from 10mg are really only from 3-7mg, then what would happen if the bioavailability of the drug is going to 100% from 30% of the standard oral tablet?

In theory, and what past history tells us of pharmacology, it would give 3.3x more of the drug and its effects, same being with its side effects. Or I can take 1/3 of the dose and get no more side effects but with the same benefits. But this is only one part of enhancing drug availability, we have not spoken about delivery methods and how it alters a drug’s strength, side effect, or time of release. Or how Even the side effects aforementioned can be dropped or lessened all because of the different delivery methods.

How is all of this possible from the same drug, just a different way of the form of administration, without the side effects of its oral counterpart? It’s all shown in the liver numerous times before SARMS with anabolic steroids, and it starts with a little protein, measured in nanograms that are found in your liver called Sex Hormone Binding globulin (SHBG). Don’t let this tiny molecule fool you because it can change you physically and mentally in a horrific way and for life with a simple nano-sized molecule that, compared to the protein we eat per day, is laughable. It’s like a basketball being compared to the size of the sun, but the basketball is carrying an atom bomb with 1000x more power, and the sun had nothing. Pay close attention below as I explain step by step how this is done, and why each step causes a side effect or lack of effect thereof.

The Metabolization of an Oral SARM

The reason for its side effects, and its mild Potency on strength and anabolism vs steroids as a PED.

What is SHBG?

SHBG, the MOST important transport protein for sex steroids in human plasma, is synthesized mainly in the liver. Plasma SHBG regulates the bioavailable fraction of steroids and also their access to the target cells. It binds strongly to three sex hormones found in both men and women. These hormones are estrogen; dihydrotestosterone (DHT), and testosterone. SHBG carries these three hormones throughout your blood to its destinations. the side effects being seen in SARMS and steroids start in the liver with this little protein (SHBG), because of how it’s being impacted/changed greatly due to when exogenous sex hormones or SARMS are given orally. Several other factors affect the synthesis of SHBG, because hypothyroidism, hyperinsulinemia, non-insulin-dependent diabetes, and a hyperandrogenic state are associated with low circulating levels of SHBG.

The “hyperandrogenic” state is one of the states that taking exogenous SARMs or anabolic steroids put us in. This literature coincides with what we are experiencing and what I am explaining here as well.

Why does SHBG matter in this process?

When levels of SHBG significantly change or over a small window of time from exogenous hormones, this leads to a shift into DHEA and its regulation by the body. DHEA is the precursor hormone that is responsible for the regulation of these hormones. When SHBG rapidly drops off or changes, the DHEA now becomes unregulated and sporadic in levels when converting into testosterone/DHT.

What is DHT? And how does this affect side effects?

DHT is a very strong agonist of the AR and is, in fact, the most potent known endogenous ligand of the receptor, about 3-fold higher than testosterone. After testosterone is converted to DHT, DHT is in turn normally metabolized into many metabolites, two of which are a relatively smaller quantity of 5a-androstane-3a,17b-diol (abbreviated as 3a-Adiol), and a usually larger amount of 5a-androstane-3b,17b- diol (abbreviated as 3b-Adiol). These same researchers also report that while nearly all the 3a-Adiol is converted back to DHT, the 3b-Adiol does not convert back to 5a-DHT. Very importantly, they report that 3b-Adiol is an anticarcinogen that activates estrogen receptor beta, an anticarcinogenic estrogen receptor present in large numbers in the prostate gland. And Estrogen receptor beta is present in many other tissues in both sexes. Aside from stimulating the estrogen receptor, some are also converting back into DHT. If this wasn’t enough of a problem, DHT is broken down into a beta 11b, hydroxyl metabolites. One of which is many folds more androgenic and harsher with side effects than DHT itself, nearly 10x! And this was all because of the change in SHBG, affecting a cascade of hormones from DHEA,

DHEA-s, DHT, estrogen, and all the metabolites produced in response. https://www.researchgate.net/figure/Conversion-from-DHEA-to-DHT- requires-3b-hydroxysteroid-dehydrogenase-3bHSD_fig1_262681222

Another issue

Cholesterol (and lipoproteins)

The liver and the passing of any sex hormone, or SARM, is the trigger to the entire cascade effect I explained earlier. The direct lowering of SHBG starting in the liver during the first metabolization of the SARM is what triggers the DHEA/DHT responses that are, in the end, responsible for the shutdown and most if not all androgenic side effects. But if that wasn’t enough, cholesterol and the correlating shifts in the brother and sister proteins called HDL/LDL are affected as well, and I’ll explain this all in order.

Cholesterol is needed for making the membrane on every cell and for building other cellular structures that are damaged during exercise. Just like the protein that was damaged during a workout through mechanical overload, the surrounding membrane also takes a hit. This is true from injections as well with scare tissue forms from the damage by the piercing needle. So even with performance-enhancing SARMS or steroids, your protein shake is almost useless if you do not get adequate cholesterol, hence why vegans still tend to lose muscle even with an excess of calories and protein. Without the membrane in not functional and even IGF is useless in hypertrophy or proliferation until these are fixed. So, it is absolutely necessary for the synthesis of hormones, vitamin D and Cell membrane synthesis. now, the HDL & LDL job is to transport all fat molecules, like triacylglycerols, or triglycerides, phospholipids, and cholesterol within the extracellular water of the body to all the cells and tissues of the body. For example, artery walls, when damaged or cut, the Lipoproteins are sent to bring the cholesterol to be glued to the damaged site. Now that you can see the correlation in elevated levels of HDL, LDL, and cholesterol, you can also the importance of these in your body, and why they take such a hit on your bloodwork and health and how it can be avoided (by modifying the drug solution for an alternative delivery method with) through a bioactive injectable SARM.

Summary

Why did I bring all this up when talking about oral vs inject SARMS?

Well, when injected, the SARM now skips the first pass of the liver (the start of the side effects). In a published finding that shows another sex hormone and its effect on SHBG because of the first pass in the liver from the oral form, vs none at all due to a transdermal patch. In its conclusion, it states: Oral but not transdermal estrogen stimulates the synthesis of SHBG in the liver. The extensive metabolization of sex hormones by the liver. A history of ICP was not accompanied by any differences in basal levels of serum SHBG, but the increases of SHBG after oral estrogen were blunted in these women.

The Injectable Sarms also do not affect hormones directly due to homeostasis regulation like anabolic steroids do, and being that they lack the metabolization into worse bi-products like those steroids, being especially of importance when dealing with testosterone shut down from oral SARMS. Then we negate most all side effects, including virilization in females, to a much higher mg/mg threshold. Now in higher amounts, these side effects should start to creep up as some level, but the dosage required to give these same results is now much less. However, now we have an actual drug that can be more accurately called a SARM.

Modified Injectable SARMS

The potential for these modified SARMS are limitless and, as far as we know, unknown possibilities in the future. When we look at these compounded versions vs their oral counterpart, we can see the massive differences in effects-benefits to their side effects.

Each SARM seems to have its counterpart to an anabolic steroid, from its anabolic/androgenic effects to its side effects. The problem with the information people is spreading on SARMS is misconstrued. The ideology behind them is that it’s said to have little to no side effects of androgenic steroids…

For example, supposedly these only work on the receptors of skeletal tissue (and bone) and produce its effects here, while having little or no androgenic effects. While this is true with the nuclear receptor of androgenic receptors, it is only true when the dosing is in very small amounts, much less than an athlete would take to see any noticeable benefits. that’s the problem, the intelligence levels in some are substandard to the point that if they could read, and they read the studies on this information, they would overlook the fact that the patients used in the study were all geriatric patients with muscle wasting/atrophy and all have very low amounts of testosterone. The dosages like .3mg, 1mg, and 3mg giving substantial muscle gains and fat loss are not even feasible in an athlete, let alone a healthy normal 180lb adult. Even with this, some SARMS definitely have androgenic side effects, like s-23 (it was made to suppress fertility), and this is more apparent when the dose increases. So, as the dosage increases, the increase in anabolism and muscle growth does as well.

ORAL SARM – increased side effects with dosage increase, but also increasing the anabolic potential and growth.

Modified Injectable SARM – Minimal to no side effects with the same dosage, while drastically increasing the anabolic effect and potential growth.

Unfortunately, there is little to no research published on these compounds other than what we have been conducting amongst our team and the researchers and doctors involved in the journey. If you think about it, we really only have the information from current and past PED’s to use as our starting point in understanding how these true function. Hypothesizing all the possibilities from what is available in past literature/knowledge with steroids and their effects is one thing. But to run the experiments and put the theories into testing through lab work, enzymatic testing, HPLC-LCMS, and trials is pioneering. So, from what we know about steroids, and from years of testing and experiments, both successful ones and the failures, here is a list of the compounds and an overview of each and its application.

Factors Influencing the Absorption and Elimination Rate of a Drug

After the injection of a drug or hormone, the fate of the drug is potentially influenced by, but not limited, to a number of factors such as the shape of the depot at the injection site, being intramuscular vs subcutaneous, if lipophilic or lipophobic drugs are being used, and the fate of the oil vehicle or other carrier vehicle by the systemic absorption of it by the body. All these influences affect the overall pharmacokinetic fate of the therapeutic agent.

The importance of these factors varies with the route of administration but always starts with the drug itself, the carrier, and delivery vesicle properties given by the modifying of the drug or solution.

We have 3 variations of modification which all change the time of absorption and clearance of the SARM. Each giving a different rate of breakdown or metabolization. The first variable we will start with is the route of delivery, being intramuscular (i.m.) route or depot injection. This is the preferred route of administration of human injections in medicine, although more stable blood levels and longer breakdown times are shown in the subcutaneous tissues of relatively similar hormones with oils. It could affect your end result is a positive or negative when it comes to hormones absorption/effects when given Sub-Q vs IM. The subcutaneous injection is normal or common practice in veterinary clinics, for credible reasons, but that’s for a later topic.

Overview of processes influencing the pharmacokinetics fate of drug substances after injection of lipophilic drug solutions. The drug would be (D), would represent the parent drug compound or SARM in this case (However, several other factors, such as the shape of the depot at the injection site and the fate of the oil vehicle per se, might affect the overall pharmacokinetic fate of the therapeutic agent)

How do we determine the half-life?

Potential Factors Influencing the Release Mechanism and Rate Factors

  • Drug partition from oil vehicle to tissue fluid – Suggested being the major factor controlling the drug release (at least for substances with moderate lipophilicity)
  • Spreading and dispersion of the lipophilic solution at the injection site – Can affect the release rate by changing the oil/water interfacial area. Variation in spreading/dispersion might be affected by injection volume, oil viscosity, interfacial tension of the oil, injection site, and injection technique.
  • Injection site – Variations of physiological factors such as blood and lymph flow, number of blood vessels, and injection depth may influence the rate and extent of absorption.
  • Injection volume – Affects the absorption rate by changing the surface-to-volume ratio of the oil vehicle at the injection site (further studies are needed).
  • The viscosity of the oil vehicle – Currently, no correlation between oil viscosity and absorption (and release) rate has been found.
  • Diffusion of the drug in oil vehicle – To be clarified.
  • Drug transport in tissue fluid by diffusion/convection – Dictate the “degree” of sink conditions in the vicinity of the injection site.
  • The disappearance of oil vehicles from the injection site – Has to be considered primarily for highly lipophilic drugs.
  • Hydrolysis of ester prodrug at the oil/tissue fluid interface – Possible release mechanism mediated by lipases.
  • Metabolic Rate – Exercise, calories in vs out all affect the metabolism of the fatty oil surrounding the drug.
  • Enzymes – One thing we can’t control is The enzymes responsible for metabolizing the substances. It varies from person to person and requires genetic testing such as the pharmacogenomics test. Some people are slow and fast metabolizers of certain drugs because of the number of enzymes they produce or don’t.

Disregarding local metabolic activity, the drug substance (or a prodrug derivative of the active pharmaceutical ingredient) can be removed from the site of administration by two different processes. The active agent may be released from the oil vehicle into the tissue fluid followed by transport to the microvessels, where the average length of diffusion to a capillary is influenced by the extent of spreading of the depot at the injection site. Alternatively, small oil drops containing the drug may be cleared from the local injection site by transport into the lymphatics. Where prodrugs are used, the site of prodrug conversion, as well as uptake into fatty tissues (“second depot”), may also have an impact on the clearance of the parent drug. But remember SARMS are active drugs, not prodrugs, so we can skip the prodrug site and go direct.

How do we calculate all of these variables?

So, with all these factors that change our absorption rates and time, it makes it impossible to get an exact half-life or elimination life of a drug. However, we can go by the standard we know to exist, from past literature with relatable steroids and drugs in similar vehicles vs oral. And if we understand that the number can and will go up and down depending on those factors listed above and find a fair medium, we can get a more accurate half-life and it can be verified from lab work on a few of these. You can also manipulate each one of these to increase or decrease these numbers, but it is inaccurately measured and too much to explain before understanding these first. The simplest way to calculate the rough Half-life on the first modified Sarm delivery is as simple as adding 16 hours, (+/- 4h)

*this changes by the half-life of parent SARM. Now, this number is used ONLY as the average. When you take every half-life of each SARM and take the half-life of the depot, combined with the time it takes for SARM to release from the depot. The problem to this is when scaling, for example, when we have a longer half-life of the active drug, the increase in clearance time does not increase at an equal rate per hour as the half-life of the drug dose, rather it affects the clearance timeless and less as the SARM’s natural half-life increases and vice versa. As it decreases, the clearance time does not go down at a constant rate. Rather, its clearance time % is longer as the SARMS half-life is shorter, effecting the time much more. Another example is LGD-4033.

We have a half-life of 24 hours naturally. The modified injectable will increase 8 hours depending on the variables. While the Yk-11 or modified Follitonic version would increase from 4 hours to 20-22 hours, again dependent on the variables.

Learn more about how injectable SARMS and Magnalone in particular work.

Watch full explanation in the video:

Part 1 – https://anabolictv.com/2019/10/magnalone-modified-injectable-lgd-4033-ligandrol-explanation-part-1/

Part 2 – https://anabolictv.com/2019/10/magnalone-modified-injectable-lgd-4033-ligandrol-explanation-part-2/