Tuesday, 24 March 2015

Crossing thresholds may permanently change you

My ranting and raving about melanotan 2 has inevitably made a few people ask me if the darkening in skin tone was long lasting or permanent. The darkening in skin tone was certainly "long-lasting" appearing to take about 9 months for me to fade back to my pale self, however there has been atleast one permanent side affect.......... I developed new freckles.

I cant say ive noticed any new freckles on my face however, just mostly on my body.

If you read other peoples personal accounts of melanotan 2, weight control doesnt seem to be listed all that often. This makes me think I may of been somewhat a super-responder to MT2. Probably because im both weight reduced .....and my obvious mc1r mutation which makes me tan resistant could indicate I have slight mutations in mc4r and mc5r aswell.

Another thing I noticed when injecting MT2 was that I usually always did the left side of my stomach and after sometime the left side appeared more deflated than the right side, making me think that MT2 might have local effects on adipocytes at the injection site. It appears there are mc5r's directly on adipocytes and that may have accounted for this effect.

Whats curious though is the permanent new freckles.

MT2 is a stronger analog of alpha-MSH, which activates melanocortin receptors, but MT2 also has a substantially longer half life.  oh and I forgot to mention, while on MT2, existing freckles went extremely dark almost to the point of black.

This was all sounding eerily familiar, and I suddenly got the idea that maybe alpha-MSH is to melanocytes as insulin is to adipocytes.

This notion is further supported by the finding that alpha-MSH actually can cause skin cells to differentiate into melanocytes, exactly like how insulin can cause pre-adipocytes to differentiate into full adipocytes.

Skin cells do not normally produce melanin, but they will do once they differentiate into melanocytes. Exactly like how pre-adipocytes do not store triglyceride,  until they differentiate into full adipocytes. BTW this explains where the new freckles comes from with MT2 use. I expect either existing stem cells and/or skin cells each have their own thresholds that must be appeased before they will differentiate into melanocytes, and my normal levels of alpha-MSH was too low to activate them

But once the super stimulus of MT2 is used, the threshold is passed, and additional cells morph into melancoytes = new freckles.  Exactly how like super levels of insulin and glucose causes pre-adipocytes to morph into full adipocytes and make you gain weight.

Even further! as I have said, the new freckles appear to be permanent, again exactly like how new fat cells in obesity appear to be permanent.

And lastly, as mentioned, MT2 caused existing freckles to become extremely dark, indicating that MT2 turbo-charged the production of melanin within these melanocytes.  Well... Lo and behold, this is very similar to what insulin does in adipocytes, it turbo-charges the production and accumulation of triglyceride.......

So,,,,, alpha MSH can cause cells to differentiate into melanocytes and cause over-production of the primary thing melanocytes are suppose to make.......melanin

And....insulin can cause cells to differentiate into adipcytes and cause them to over-produce the primary thing they are suppose to make........triglyceride.

What a coincidence..............

Anway,    there are other areas in biology where crossing thresholds seems to produce irreversible changes. Females that take exogenous androgens ( steroids ) become "permanently" masculinized. .  And its possible that satellite cells permanently morphing into myocytes may account for the phenomenon of "muscle memory" that most bodybuilders swear by.

In both of those cases we are again relying on certain hormones to cross threshold levels.


  1. Interesting and insightful blog entry.

    a-MSH is to melanocytes as insulin is to adipocytes, indeed.

    After one is exposed to supraphysiologic insulin, one is permanently obese and must starve themselves, even on a ketogenic diet, to "appear" normal sized.This is due to profuse adipocyte hyperplasia from the prior insulin stimulus.

    As well, if one is exposed to even a short course of a-MSH , one has new melanocytes and freckling is observed. This is permanent and cannot be undone even when a-MSH returns to baseline.

    Other examples of permanent hormonal modification of hte body:

    -Androgens and a male like appearance (as you described, females exposed to even mild testosterone excess forever wear scar of masculine bone structure, even if she reverts to female endocrine system).

    -Growth hormone excess and acromegaly. Mike Cernovich and various other juicers have almost a cave-man like look , coarse thick features and hands from chronic abnormal growth hormone, which is permanent. Body builders develop heart failure and enlargement of the internal organs, which creates a distended abdomen (termed "palumboism" amongst body builders). The fluid backup into venous circulation from heart failure (a consequence of GH use) as well as GH effects on organs leads to a pot belly bloated look.

    -Cortisol excess permanently damages the body, adipocytes are laid down around waist, bones and skin lose their proteins.

    -Progesterone causes female aging from an aesthetic perspective. It darkens the skin, thickens the waist, raises body fat, ruins glucose metabolism largely permanently. Women who have had children will always appear older relative to women who have not had children other things equal.

    Actually it is more the rule rather than the exception that all the hormonal and nervous system signals in the body induce some kind of permanent immutable effect.

  2. kindke, do you think there will ever be a cure for obesity? and if so, when? i lost 12 kilos and its so tiring trying to keep it off. but i know the alternative is being treated like crap by everyone else at school. please give me hope :(

    1. Dont think there will ever be an exact cure, not for a VERY ( not within next 50 yrs ) long time atleast.

      However there are some drugs on the horizon which should surely help. mc4r agonists and fexaramine is a bile acid receptor agonist which should be quite useful. I think 5-10 yrs and you will these available and while they wont cure obesity they should certainly help you stay at a lower weight.

      In the meantime though, in the next 1-4 years I dont see anything coming out. Your best bet is to stay low carb and exercise and try your best to keep the weight off. IF you end up regaining weight try not to blame yourself. Genetics and epigenetics account for about 85% of your weight and that is not fightable with lifestyle interventions.

  3. What's your thoughts on leptin injections? Do you think these would keep the weight off or do you think they get rid of adipocyte cells?

    1. ive been doing a bit more research on leptin recently and hope to have another post on it soon.

      in short, im of the opinion leptin is absolutely critical to anyone attempting to lose weight through dieting. So much so that im starting to think that dieting without leptin replacement is completely pointless because lost weight is regained in 80-90% cases. I have regained weight a few times myself and I can certainly appreciate how hard it is to keep off.

      if by some miracle you can actually get leptin then yes it will help WITHOUT any doubt, but as im aware its extremely hard to get and expensive to manufacture aswell.

      I havent seen anything to suggest leptin injections cause fat cell loss , apart from a bolus dose of leptin injected directly into the brain, which you wont be able to do ofcourse. Although I remain hopeful, at this point in time there is nothing im aware of that can be practically used to reverse fat cell multiplication in humans.