SARM S-4 dose being used are TOO HIGH!!

[cvictorg]

I think that the yellow vision and impaired night vision that people are reporting are side effects of acute overdose of S-4.

The only clinical trials on S-4 are the ones that GTx is doing for Ostarine (their brand name for S-4). But their clinical trials used up to 3mg TOTAL per day, not per kg of bodyweight per day. That's a difference of a couple orders of magnitude. The dosing for this chemical has been WAY too high, because one of the primary people selling it does not understand the research.

GTx Presents Phase II Ostarine (MK-2866) Cancer Cachexia Clinical Trial Results at Endocrine Society Annual Meeting

This preliminary study on S-4 in rats found that anabolism in muscle was maxed out at around 0.75 mg or 2.82 mg/kg per day

Pharmacodynamics of Selective Androgen Receptor Modulators
PubMed Central, Fig. 5: J Pharmacol Exp Ther. 2003 March; 304(3): 1334–1340. doi: 10.1124/jpet.102.040840.

When corrected for body surface area and converted to dosing for humans, the dose that maxes out the anabolic response would be around 0.46 mg/kg. In a 200 lb male, that works out to about 40 mg/day. That may sound low, but it's still 13 times higher than the highest dose they used in the clinical trials. You sure as hell don't need hundreds of mgs per day.

Here's a paper on converting animal doses to humans

Dose translation from animal to human studies revisited -- Reagan-Shaw et al. 22 (3): 659 -- The FASEB Journal

As the abstract states, "The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight..." The FDA has stated that the extrapolation of animal dose to human dose is correctly performed only through normalization to body surface area. To convert mg/kg in rats to mg/kg in humans, you multiply by 0.162 (6/37). For mice to humans, multiply by 0.081 (3/37). There are several other values for other animals.

So I really don't think one needs to take 100 or more mgs of S-4 per day

Comments appreciated

[magaton]

Interesting post, somthing I've been thinking

[OH REALLY]

well i dont have a coment but i need one so..hmmmmm idk

[endus]

So I really don't think one needs to take 100 or more mgs of S-4 per day

Comments appreciated

I don't think the research is mis-interpreted - this has come up before and discussed in this and many other forum, which is where I assume you got that.

It is true that dosage is higher than what was in the study but I think you are dealing with a target group that is slightly out of normal range.

For example, your body normally produce around 70mg of testosterone naturally (going by memory so don 't shoot me) but if you noticed, most people here are taking 500mg as a starting point for newb and more experienced users doing 700-1000mg+, not including many other substance that is stacked on top.

As for S4 studies, at 3mg per day, it noted a very small LBM gain over 3 months period - not the kind of result people are looking for in this group.

Still you could do the math - at .75mg to 2.82mg per kg and using the formula of 0.162 - for 200 lb man would equal to 11.05mg to 41.5mg/day. At low dosage, its 10x with about 2.5x for higher figure for 100mg per day usage. I would say most people in this group will go with higher figure and 2.5x above study is not very high considering what they take for other substances. Not saying its right or wrong - just setting the playing field for a particular target group. cheers

[cvictorg]

I don't think the research is mis-interpreted - this has come up before and discussed in this and many other forum, which is where I assume you got that.

It is true that dosage is higher than what was in the study but I think you are dealing with a target group that is slightly out of normal range.

For example, your body normally produce around 70mg of testosterone naturally (going by memory so don 't shoot me) but if you noticed, most people here are taking 500mg as a starting point for newb and more experienced users doing 700-1000mg+, not including many other substance that is stacked on top.

As for S4 studies, at 3mg per day, it noted a very small LBM gain over 3 months period - not the kind of result people are looking for in this group.

Still you could do the math - at .75mg to 2.82mg per kg and using the formula of 0.162 - for 200 lb man would equal to 11.05mg to 41.5mg/day. At low dosage, its 10x with about 2.5x for higher figure for 100mg per day usage. I would say most people in this group will go with higher figure and 2.5x above study is not very high considering what they take for other substances. Not saying its right or wrong - just setting the playing field for a particular target group. cheers

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040234/#R9

Analysis of variance showed no significant difference in the CL of S-4 at doses of 0.5, 1 and 10 mg kg−1 ( p>0.05). Previous in vivo studies in the present authors' laboratory showed that the dose required to restore the levator ani muscle weight in castrated animals, an indicator of anabolic activity, compared with that of intact animals was less than 4 mg kg−1 day−1 (Yin et al. 2003). Thus, S-4 demonstrates linear pharmacokinetics within the dose range needed to exert maximal pharmacological effects.

The lack of parent drug in the urine suggests that S-4 is extensively metabolized. Assuming a hepatic blood flow of 13.8 ml min −1 in the rat (Davies and Morris 1993), the hepatic extraction ratio of S-4 would be less than 0.05. Based on this hepatic extraction ratio, a greater than 95% bioavailability (i.e. less than 5% of the drug would be removed by first-pass metabolism) is predicted. The present results confirmed this prediction, as S-4 was completely bioavailable following pharmacologically relevant doses (i.e. doses ≤ 10 mg kg−1).

The CL of S-4 at a dose of 0.5 mg kg−1 (1.92 ml min−1 kg−1) was significantly ( p<0.001) greater than that observed for the 30 mg kg−1 dose (1.00 ml min−1 kg−1). These data suggest that saturation of the drug-metabolizing enzymes might be occurring at this higher dose. Therefore, one would expect to see further suppression of CL following doses greater than 30 mg kg−1. However, due to the potency of S-4, the authors do not anticipate the need for such high doses during clinical use. Forthcoming data from the present authors' laboratory will provide needed information about the hepatic metabolism and pharmacokinetics of S-4 in this and other species.

The pharmacological activity and pharmacokinetics of S-4 in rats suggest that this compound has the properties of an ideal SARM as defined by Negro-Vilar (1999). It is rapidly absorbed following p.o. doses (tmax, 48−84 min), and it exerts tissue-specific anabolic effects in vivo, with anabolic effects in muscle and bone but lesser effects in the prostate and seminal vesicles (Kearbey et al. 2003, Yin et al. 2003). These properties coupled with forthcoming reports from the present authors' laboratory about the pharmacological effects of S-4 in other pertinent animal models and its pharmacokinetics and metabolism in dogs and humans, favour the continued development of S-4 as an orally bioavailable non-steroidal SARM.

So at a dose of 4mg/kg/day (using the dose conversion of .162 for rats) you're looking at a dose of appx 65mgs/day - still much less than the 100+mgs/day some here are using

BUT - at a dose of .5mgs/kg/day - you're only looking at a dose of appx 8mgs for a 100kg human!

[elpropiotorvic]

During clinical use is very different than during musclebuilding for personal reasons.....

Look at trial with other substances....But I do think that somebody oughta try it at 50 mg a day for 4 or 5 weeks or even a whole cycle...

[endus]

So at a dose of 4mg/kg/day (using the dose conversion of .162 for rats) you're looking at a dose of appx 65mgs/day - still much less than the 100+mgs/day some here are using

BUT - at a dose of .5mgs/kg/day - you're only looking at a dose of appx 8mgs for a 100kg human!

Some are using 50mg or less and still have the vision issue. I've started at 50mg and sides came after 2 1/2 days - hard. Try 25mg to see if that does it.

[cvictorg]

Some are using 50mg or less and still have the vision issue. I've started at 50mg and sides came after 2 1/2 days - hard. Try 25mg to see if that does it.

That proves my point - the clinical doses used are no more than 3mgs per day - why would you start at 50mgs per day??

Per a supplier - 1 mg equals 10 drops

The CL of S-4 at a dose of 0.5 mg kg−1 (1.92 ml min−1 kg−1) was significantly ( p<0.001) greater than that observed for the 30 mg kg−1 dose (1.00 ml min−1 kg−1). These data suggest that saturation of the drug-metabolizing enzymes might be occurring at this higher dose. Therefore, one would expect to see further suppression of CL following doses greater than 30 mg kg−1. However, due to the potency of S-4, the authors do not anticipate the need for such high doses during clinical use.

So at a dose of .5mgs/kg/day (using the dose conversion of .162 for rats) you're only looking at a dose of appx 8mgs for a 100kg human!

Why not start with that - say 2 doses of 40 drops mixed with OJ or 3 doses of 27 drops??

[endus]

Like I said, let us know how it is at that dosage. We won't know for sure until you try it. There's only so many people who are doing/logging at this point to know what is right/wrong/conjecture/myth, etc.

For me, I've started at 50mg, didn't feel anything other than sides at day 2.5 and still nothing after day 8 (remember 1/2 life of this thing 4 hours). So I could of continued at that point to find out if there's any improvement or up the dose like other people who had some strength gains. I followed their example (90-100mg) and felt my strength increase quite a bit - almost near instant (like next day on).

Because of the efficacy or half life of S4, I have a feeling that gradual buildup of low dosage might not work - but again, its only a conjecture at this point. I would love to find out - unfortunately, I'm ending my cycle this week. cheers!

[endus]

During clinical use is very different than during musclebuilding for personal reasons.....

Look at trial with other substances....But I do think that somebody oughta try it at 50 mg a day for 4 or 5 weeks or even a whole cycle...

Heck, if it wasn't for my high body fat, I would be doing Test E cycle at this point - can't even compare. I would take 500+mg of Test than S4 - dosage be damn

[bass]

Heck, if it wasn't for my high body fat, I would be doing Test E cycle at this point - can't even compare. I would take 500+mg of Test than S4 - dosage be damn

me too, that’s why i am waiting until next summer, besides, i need more training...

[tballz]

Yea well nothing will compare to good ole test.

I'm thinking SARMs might be best used for pct.

[Steroidman99]

Like I said, let us know how it is at that dosage. We won't know for sure until you try it. There's only so many people who are doing/logging at this point to know what is right/wrong/conjecture/myth, etc.

For me, I've started at 50mg, didn't feel anything other than sides at day 2.5 and still nothing after day 8 (remember 1/2 life of this thing 4 hours). So I could of continued at that point to find out if there's any improvement or up the dose like other people who had some strength gains. I followed their example (90-100mg) and felt my strength increase quite a bit - almost near instant (like next day on).

Because of the efficacy or half life of S4, I have a feeling that gradual buildup of low dosage might not work - but again, its only a conjecture at this point. I would love to find out - unfortunately, I'm ending my cycle this week. cheers!

Have you ever taken steroids ? Do you realize that it takes at least 10-14 days to see results?

[endus]

Have you ever taken steroids? Do you realize that it takes at least 10-14 days to see results?

Yes I have - actually ran couple of cycles in my 30's (for longer than what is recommended now), bunch of PH that I can't even remember their names in my 20's, and did a mild havoc/bold cycle few months ago (40's) which did some damage to my joint that I'm still recovering from.

And the difference is, efficacy is quite different - have you ever seen any Testosterone side effect coming on strong at 2 1/2 days?

And you could run your Steroid cycle for longer period. Only thing that will change that is the vision issue. If some could find a solution, it would be near perfect.

[chucklesmcgee]

The only clinical trials on S-4 are the ones that GTx is doing for Ostarine (their brand name for S-4). But their clinical trials used up to 3mg TOTAL per day, not per kg of bodyweight per day. That's a difference of a couple orders of magnitude. The dosing for this chemical has been WAY too high, because one of the primary people selling it does not understand the research...

So I really don't think one needs to take 100 or more mgs of S-4 per day

Comments appreciated

I definitely appreciate the perspective, and it's one I've voiced on a few occasions on this forum. The clinical research definitely points to the fact that very low doses of S4, doses well below what anyone has yet to identify side effects at can significantly increase muscle mass. The first phase II study used elderly men and women, people who are normally losing muscle mass over time, no special diet, no exercise protocol, and still got significant increases in LBM, decreases in fat mass and improvement in aerobic power (some stair-stepping task) at 3mg/day of S4 for a few weeks.

Keep in mind the philosophy of these clinical trials though. GTx conducted the trials to get S4 approved to treat muscle sarcopenia (muscle wasting)- not to identify the most potent dose of S4 for xbawks-hueg muscles. They wanted to identify the lowest dose possible to stop muscle loss in the elderly, and to show that minimal (none identified so far, really) side effects exist at those dosages. The FDA slaps an approval on this 2,3 years down the line, suddenly Doc's got something a lot better to help Grandma than steroids , and GTx rakes in millions. Lower doses equal less chance of side effects and lower cost per dose of S4 for GTx, so it just makes sense to invest in clinical trials that way.

Animal studies have been much more able to look at toxicity/total muscle mass gained, because let's face it, you can **** around with rats all day and no one cares. Those results may hint at a ballpark of optimal S4 doses for maximum muscle building--and you'll be able to see what happens with way too much. And I think you're right that some people are trying way too much. I see people taking 3+mg/kg and it seems a little stupid. I don't think the side effects at that level are going to be serious from what we've seen, but it would be expensive and ultimately may be wasteful.

We'll see in time what the optimal dose is.

[toothache]

We'll see in time what the optimal dose is.

Yep...the more people use it at different doses is when we will know for sure.

[freakinhuge]

I have seen people using anywhere between 100-150 mg, and that sounds way too high. I was thinking of running some for 4 weeks of 25-50 mg per day.

[anabollocks]

I finish my alpha-e at the end of next week, so this week ive started taking 20mg a day split into 2 doses of s-4, i agree the doses people are taking seem way too high, but i'll let people know how it goes at the low dose im taking.

[bass]

I finish my alpha-e at the end of next week, so this week ive started taking 20mg a day split into 2 doses of s-4, i agree the doses people are taking seem way too high, but i'll let people know how it goes at the low dose im taking.

yes please let us know, but you may have to be on that dose for longer than two weeks to notice any difference.

[anabollocks]

yes please let us know, but you may have to be on that dose for longer than two weeks to notice any difference.

yes i was planning on running it for 4 weeks.