All Posts By Muscle Insider
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Can MK-677 Cause Brain Damage? | The Effects Of Chronic Ghrelin Exposure
It is theorized in the community that MK-677 can cause brain damage via chronically elevating ghrelin levels in the body.Does this crossover to human use, and has it been observed to date?Well, there have in fact been links established between chronic ghrelin exposure and negative mental outcomes.I did cover this briefly in my original post.How applicable is this in humans though?[embedded content]Table of ContentsMK-677 Enhances Fear In RatsOne study on rats evaluated if MK-677 can cause enhanced levels of fear.There is evidence to support that one of the ways ghrelin is modulated is through exposure to stress.What this study intended to assess specifically was if rats would have a greater likelihood of experiencing fear and posttraumatic stress disorder (PTSD) when their ghrelin levels are artificially raised 24/7 with a ghrelin receptor agonist (MK-677).Rats were continuously administered MK-677 and frightened constantly, and their difference in response (MK-677 treated vs non treated) was assessed.The rats with chronic ghrelin elevation were found to have enhanced fear memory compared to baseline [R].Like I mentioned, there’s evidence to support that one of the ways ghrelin is modulated is through exposure to stress, and this study was able to stir up quite a bit of controversy in the community with its results showing a blatantly negative effect on the amygdala where the fear-enhancing effects of repeated ghrelin receptor stimulation seemed to be concentrated in.Ghrelin and growth hormone act together in the amygdala to enhance fear, at least in this rodent model.How Does MK-677 Work?If you don’t already know, ghrelin is the hunger hormone.As you would expect, ghrelin levels are high before meals, and low after finishing meals.This is how your body regulates its appetite and knows when to eat and when to stop eating.GHRP’s and GH secretagogues don’t just signal GH secretion, some also have a very significant effect on ghrelin.The most notable being GHRP-6 and MK-677.These are both notorious as appetite stimulating compounds.This is why peptides like GHRP-6, GHRP-2, and secretagogues like MK-677 cause such a drastic spike in hunger.When you use them, you’re basically tricking your brain into thinking you’re hungry when you otherwise may not be.Growth hormone is secreted by the somatotrophes of the anterior pituitary gland in multiple pulses each day.Growth hormone is released into the blood stream and then stimulates the liver to produce insulin-like growth factor-1 (IGF-1), which stimulates linear growth before epiphyseal fusion and also exerts several metabolic effects throughout life.After ingestion, MK-677 increases somatotrophe secretion of GH via signalling the pituitary gland to secrete a sufficient amount of growth hormone [R, R].The most common cause of GH deficiency in childhood is believed to be caused by a lack of adequate stimulation of the pituitary gland by hypothalamic GHRH, which is why something like Ibutamoren which can systemically increase IGF-1 levels for 24 hours with a single oral dose is very promising for potential clinical use [R].The likely mechanism of action following MK-677 administration is the activation of the ghrelin receptor by MK-677, with feedback by IGF-I preventing excess GH production [R].The mechanism of action through which MK-677 promotes GH secretion is comparable to growth hormone releasing peptides like GHRP-6, GHRP-2, Ipamorelin and Hexarelin, with GHRP-6 being the most similar in regards to the amount of ghrelin secretion that occurs post-administration.MK-677 does not stimulate a greater quantity of secretion events per day (number of GH pulsations), but rather it stimulates a greater total 24 hour GH production rate [R].In other words, Ibutamoren can substantially increase the strength of each GH pulsation that occurs in the body.Effects of treatment on 24-hour mean GH and IGF-1 and GH secretory dynamicsWas This Study Flawed?Rats chronically exposed to ghrelin were found to have enhanced fear memory compared to baseline.There is some confusion around exactly how this test was carried out, and the reality is that the rats weren’t getting MK-677 infused into their brains off the bat like many seem to think.In this study, rats were injected with 1ml/kg (i.p.).I.P. stands for Intraperitoneal injection, and is the injection of a substance into the peritoneum (body cavity).The peritoneum is the serous membrane forming the lining of the abdominal cavity.This is where MK-677 was first administered to evaluate whether increased activation of the ghrelin receptor is sufficient for enhancement of fear memory.After they established that activation of the ghrelin receptor is indeed sufficient for enhancement of fear memory, they then proceeded to infuse MK-677 directly into the basolateral complex of the amygdala to determine whether repeated ghrelin receptor activation in the basolateral complex of the amygdala is sufficient to enhance fear memory.Repeated intra-amygdala ghrelin infusions enhanced fear memory [R].Now, while this all paints a pretty bad picture for MK-677 at a first glance, keep in mind that this study also showed that a single injection of a ghrelin receptor agonist was not sufficient to enhance fear, and even chronic ghrelin receptor agonism did not alter locomotion, innate anxiety, or the expression of previously acquired fear memories [R].How Applicable Is This In Humans?In humans, MK-677 has been found to be well tolerated for over a year straight using 25 mg per day orally.Humans aren’t injecting this compound, and they certainly aren’t infusing it into their brains either.This finding has yet to be replicated in human trials, or even in anecdotal logs to date.With that being said, are they looking for this in the human data?Probably not, and obviously those using MK-677 recreationally aren’t getting brain scans before and after their use.You probably shouldn’t be chronically exposing yourself to ghrelin in the first place for years on end if you can avoid it.There are auto-regulating mechanisms in your body for a reason.It would be wise to err on the side of caution and cycle MK-677 if you are going to use it anyways, regardless of what the data may or may not imply.Even if there was no neurological risk, I would still advise cycling MK-677 if you are going to take it because of its effect on insulin sensitivity, which I think is a more immediate concern than any extrapolated claims about its effects on brain health.What I’d Be More Concerned With – Insulin SensitivityWe already know that MK-677 and exogenous GH can negatively impact blood glucose control, and we already know that poor blood glucose control is one of the main issues that cascades into the majority of health problems we see widespread nowadays.Chronically elevating your blood sugar with MK-677 is going to have a negative impact on your insulin sensitivity to some extent.Although several clinical studies found no change in blood glucose levels, there were a couple studies where MK-677 caused an elevation of fasted blood glucose levels and decreased insulin sensitivity [R, R].GH causes blood sugar levels to rise, which in turn requires the pancreas to work harder to compensate and release insulin to bring blood sugar levels back down to homeostasis.Chronic GH elevation can create chronic pancreatic stress in certain scenarios, which eventually can result in pancreatic beta cell degeneration, and insulin resistance.Chronic blood glucose elevation and pancreatic cell degeneration is what eventually leads to Type 2 Diabetes.Individuals with other lifestyle factors that contribute to insulin resistance as is (excessive carbohydrate intake, holding too much body fat, lack of exercise, etc.), or have genetic predispositions that increase their likelihood of Diabetes, could potentially end up pushing themselves over the brink and become Type 2 Diabetic with MK-677 or synthetic growth hormone usage.MK-677 can also cause reverse hypoglycemia in insulin resistant individuals.When MK-677 or GH raises blood glucose levels, this is autocorrected and regulated by the pancreas in healthy individuals.In insulin resistant individuals, MK-677 can cause reactive hypoglycemia, whereby sharp spikes in blood sugar can cause an exaggerated level of insulin secretion and glucose uptake into the cells, consequently crashing blood sugar and causing hypoglycemia [R].This poor endogenous regulation of blood glucose levels is typically indicative of some degree of insulin resistance in an individual.Signs and symptoms of reactive hypoglycemia may include hunger, weakness, shakiness, sleepiness, sweating, lightheadedness and anxiety.I believe that long-term MK-677 use will probably force you to to implement blood sugar control strategies that you wouldn’t have needed to otherwise.If you’re a borderline type II diabetic to begin with, and you throw MK into the mix long-term, that could easily push you over the border.For somebody completely healthy, you could potentially take yourself from completely healthy to like mildly insulin resistant if you deploy MK for years straight without breaks.Much like the same occurrence if you used a high dose of growth hormone for a long span of time, it would impede your blood glucose control to some degree.This doesn’t mean that you can’t use MK-677 or exogenous GH without developing insulin resistance, I’m simply asserting that you will likely have to keep a closer eye on your blood sugar, and may have to start incorporating certain strategies into your lifestyle that you may have not needed to otherwise to remain as healthy as possible while using it.Getting back to the effect MK-677 has on stress and fear, I don’t think it’s going to cause any notable mental degradation, and all of the clinical data and anecdotal logs seem to reinforce that.With that being said, throwing a wrench into your stress feedback loop may have deleterious outcomes that we are simply not evaluating with accurate metrics, and with that in mind, it would be wise to cycle MK-677, especially if it is being used for performance enhancement and not to treat a GH deficiency.If it is being used therapeutically for GH deficiency, obviously that is a different story.Monitor Your Glucose Control And Insulin SensitivityI think the more immediate concern when it comes to MK-677 is insulin resistance rather than the speculated neurological degradation that doesn’t seem to occur with its use in practical application at commonly used dosages in humans.We do know MK-677 has a notable impact on blood sugar not just in the long-term, but immediately following its first administration.In addition, the excessive amounts of ghrelin MK-677 causes the body to secrete will cause overeating in many individuals.The population is fatter than ever, and has already shown that they have horrible self-control when it comes to refraining from overeating.Add a ghrelin receptor agonist on top of that that literally tricks their brain into thinking that they are even hungrier and you can just imagine what the outcome of that would be for the average guy.In my opinion, this is the main concern with MK-677, not fear memory enhancement.If you are going to use MK-677 or exogenous GH, keep a blood sugar monitor on hand and keep a close eye on your fasting blood glucose levels, your blood glucose control post-meals, and incorporate lifestyle, diet, or supplement protocols that will prevent the excessive amounts of ghrelin and spike in GH/IGF-1 from impairing your health status.MK-677 has a lot of therapeutic promise, and can even enhance a performance enhancing protocol significantly if used correctly.Knowing how to minimize your risk profile while you use it though is critical and should be well thought out before you haphazardly start taking it without any prior research.Where To Buy MK-677Most 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 or MK-677 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 MK-677: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
Does Lactobacillus Reuteri ATCC PTA 6475 Probiotic Help Prevent Hair Loss? | My Review
Lactobacillus Reuteri ATCC PTA 6475 is a strain that was hyped up in the community after an article was published called “Probiotic ‘glow of health’: it’s more than skin deep” [R].In the article, you can see that the mice that were fed with this probiotic strain experienced significantly better hair growth, and also exhibited a much more favorable ratio of anagen to telogen hair cycle stages.The majority of the article elaborates on how promising this probiotic strain is for hair growth, skin health, as well as overall health in general.Of course, I had to try this myself to see if there was any crossover in humans.[embedded content]My Experience With Lactobacillus Reuteri ATCC PTA 6475It was really hard to come across to find this exact strain.After digging for several hours, I found one company that sells it.I bought several months worth and took it diligently every single day.After using it for several months, I can confirm without a shadow of a doubt that it made no noticeable difference on my growth rate.Obviously, these images and results look really promising.When you see a mouse experience significant improvement in their hair growth with the only factor changed being this probiotic, you can’t help but assume this is very encouraging data.But, not everything in rodent studies translates into humans, and this is one of those cases where the probiotic I don’t think is worth adding to your regimen.My VerdictSave your money.The Lactobacillus Reuteri ATCC PTA 6475 probiotic strain doesn’t work well for hair loss prevention, if at all.With that being said, I’m not asserting that probiotics aren’t good for health.Good gut health does have some impact on levels of shedding, and potentially even androgenic alopecia in general.Inflammation and the inflammatory response in your scalp is obviously tied to your gut health at the end of the day.But, as far as the potential of this strain in particular inducing a unique growth effect that you wouldn’t get otherwise get, it just isn’t the case.Related
Oral Castor Oil For Hair Loss Review – My Experience And Others
After I made my first oral castor oil for hair loss post a couple of months ago, I received hundreds of DM’s, private messages, YouTube comments, emails and tweets asking me to post an update.Well, here it is.After trying oral castor oil for hair loss for 2 months, I have concluded that it is an effective growth promoter, and is far more potent than topical castor oil.Is it more effective than Minoxidil as a growth promoter?No, however, it has a more tolerable side effect profile, is far cheaper, and provides results that are at least noticeable enough to justify it being worthwhile to explore further.There are VERY FEW compounds that can effectively promote a healthier rate of growth.The 2 most effective in my opinion are Minoxidil and MK-677.However, that doesn’t mean that they are sustainable long-term options for every one.With Minoxidil, circulatory issues can be a major problem for some, and with MK-677, glucose control and insulin resistance may pose an issue with long-term use.When considering the side effect profile for micro-dosing oral castor oil for hair loss, the worst side effect I have heard of so far is an upset stomach.Fortunately, if your digestive system doesn’t agree with castor oil, it is pretty easy to tell and immediately lower your dose, or discontinue your use.This is what I noticed personally using at least 1 mL per day for 2 months straight.[embedded content]Table of ContentsOral Castor Oil and Digestive IssuesWhen it comes to digestive issues, I’ve had none so far using as much as 1.5 to 2 milliliters per day.On a typical day I will just take 1 mL, but occasionally I will bump it up.There is no rhyme or reason to it, I just want to see how well I can tolerate up to 2 mL, but then some days I decide I probably don’t need that much and should stick with 1 mL.When I first started researching about oral castor oil for hair loss, there were a few guys who suggested that there is a point of diminishing returns once you hit 2 mL, and anything above that starts to put you into laxative territory.However, as more and more people have tried this, it seems more likely that there is a dose dependent improvement in results.So, there is a possibility that the more you can tolerate the better it will be for hair, but that will be individual dependent at the end of the day, and will only be determined via personal experimentation.Gut health is very sensitive.Some people can’t even drink a cup of milk without destroying their guts, and then some people have iron stomachs and can eat like crap and be fine.This is all individual dependent at the end of the day.I will probably try tapering up in the future to see how high I can get my daily dose without digestive distress.Despite the fact that I haven’t had any digestive issues as of yet, that doesn’t mean that it isn’t common.Over the past few months, I’ve spoke with dozens of individuals who have also tried oral castor oil for hair loss.While the majority of them found that it was effective, a handful of them discontinued because of gut issues.If you have compromised gut health as is (actually pretty common), adding castor oil on top of it probably won’t help.I would recommend optimizing your gut microbiome before you start taking oral castor oil, as it is fairly common to cause digestive distress, even at low dosages.In general, it seems like most are having fairly good outcomes with high levels of tolerability.One of my friends did actually discontinue because he thought that the quality of his sh*ts had started to show signs of digestive issues.However, he was taking 5 mL per day.In addition to that, his diet isn’t 100% on point.As mentioned, for me there’s been no difference, so far.I’m keeping it in my protocol for now and for the foreseeable future.A Glowing Review Sent In By A SubscriberI received this email shortly after posting my first video on castor oil and felt that it was worth including in this post.His personal information is redacted for privacy.Since I posted this article, a couple testimonials were commented on the YouTube video that I felt were worth including as well. My ResultsI do think that oral castor oil has positively impacted my growth rate to a notable degree.I definitely have to shave more often and get my hair cut more frequently now.I think my hair might even be getting a bit darker too, but that could just be me seeing things.It’s definitely growing quicker though without a doubt.Mainly what it seems to do well is offset the cosmetic look of hair loss.By improving your rate of growth relative to your rate of loss, you can create a more favorable ratio of hair follicles in the anagen phase relative to the catagen phase.While this isn’t directly preventing further loss be addressing the root of the issue, it can help you keep more hair on your head, and ultimately maintain a fuller head of healthy hair.If you’re a diffuse thinner, the benefits of oral castor oil will be even more evident as your issue more or less boils down to a horrible ratio of catagen to anagen activity.Keep in mind, if all you’re using is growth promoting agents like Minoxidil or oral castor oil, you’re fighting an upstream battle.The best strategy in my opinion is to lower your rate of loss as much as you can with compounds that address androgens directly, and then stack growth promoting agents on top of that.If you only use growth agonists like Minoxidil, you will eventually run into the inevitable problem where androgen induced miniaturization has progressed so much that the artificial increase in circulation you’ve induced with Minoxidil is no longer sufficient to offset your loss of hair density.Androgens are still wreaking havoc on your hair even when Minoxidil is in your system if you do not have something in your protocol that addresses androgens directly, or a part of the cascade that occurs as a consequence of androgens.Simply increasing circulation with a potassium channel opener is not going to be sufficient to stave off androgenic alopecia.I use the analogy of trying to row a canoe up a stream against the current to describe hair loss prevention.If you try to row against the current, you might be able to hold your ground for a while, but you’re fighting an uphill battle and the current doesn’t stop.Ideally what you would do is get the current to stop before you even get in the water (things like anti-androgens, 5-alpha reductase inhibitors, SARMs, Estrogen modulation, PGD2 inhibitors, etc.), and then get in the water and deploy your growth agonists as needed based on risk profile and tolerability (microneedling, oral castor oil, Minoxidil, growth hormone secretagogues, etc.).With that being said, growth promoting options that appear to be fairly low risk (like microneedling) make sense to deploy concurrently with whichever strategy you have in mind for tackling androgens off the bat.Castor Oil Long Term Safety ProfileTolerability as a laxative sheds light on the safety of micro-dosing oral castor oil for hair loss prevention in the short term, but in the long term, that remains to be seen.According to the Food and Agricultural Organization and World Health Organization, up to 0.7 milligrams per kilogram of castor oil per day is safe for men [R].Oral castor oil is also generally recognized as safe and effective for use as a stimulant laxative by the FDA.I’ve been using one milliliter per day on average, which is next to nothing by clinical standards.Women are given upwards of 60 milliliters in a single dose to induce labor [R].For constipation in adults, 15-60 milliliters in a single dose is commonly prescribed and generally recognized as safe [R].Minoxidil Vs. Castor Oil EfficacyMinoxidil is a more effective growth promoter than oral castor oil.However, oral castor oil seems to have a much better side-effect profile. In addition, this isn’t a one or the other choice that needs to be made.They can be used in conjunction with one another for an even better effect.When you compare them to one another, Minoxidil will win hands down in efficacy.However, oral castor oil will not cause you to shed horribly when you start it, and it also won’t cause a massive shed if you stop taking it.Both of which are huge limitations of Minoxidil.Minoxidil use backs you into a corner, and you have to think long and hard before you introduce it into your protocol as it can be very mentally taxing to make it through the initial shedding phase, and if you encounter intolerable side effects, you will have another shed when you stop using it.In addition, forcing the potassium channels to open more can have deleterious outcomes on the cardiovascular system, and it isn’t uncommon for individuals to report premature aging of their skin with Minoxidil as well.Those are two massive limitations of its use that oral castor oil does not seem to have.Don’t get me wrong, Minoxidil can be a great addition for some individuals, but it is certainly not a low-risk treatment and should be approached with caution.The only limiting side effect of castor oil that I’m aware of as of now is its gastrointestinal effects that may not be tolerable for all individuals.Other than that, it’s extremely cheap, seems to have a very favorable risk profile, and is at least in the same ballpark as Minoxidil in regards to efficacy.That is more than you can say for any other growth promoting agent out there with a stamp of safety approval by the FDA.The only other growth promoting agent I can think of off the top of my head that’s formidable to Minoxidil and oral castor oil is MK-677, or literal growth hormone injections.But, is that really a long-term sustainable practice just for hair density?Ideally, you don’t want to potentially put yourself in a state of compromised blood glucose control just so you can get a better growth rate on your head.When it comes to growth promoting agents, I believe that oral castor oil is one of the most cost-effective and well-tolerated options there is for a beginner.Oral Castor Oil Vs. PGE2 Applied To The ScalpThe reason oral castor oil works is the Ricinoleic Acid in it that increases PGE2 in the body as discussed in my first post.Logically, one would assume that using straight PGE2 instead of oral castor oil would be even more effective for hair growth, as the end goal of using castor oil in the first place is increasing PGE2 in the body.In practical application though, oral castor oil actually seems to work better than literal topical PGE2.In the past, I would microneedle my scalp with the Derminator (a microneedling device) set at 1.5 mm and then apply straight PGE2 to my scalp afterwards.In theory, this seems like a great idea to tip the scales in the body to a more favorable PGE2 to PGD2 ratio.After a lot of experimentation, I believe that oral castor oil is superior for a few reasons.The first being that PGE2 is extremely expensive.Castor oil is literally 1/1000th the price (maybe even less).In addition, PGE2 is measured in such small quantities (micrograms) that trying to avoid overdosing it while still getting sufficient scalp coverage is near impossible.By using castor oil, you give your body the ability to regulate how much PGE2 it converts, rather than overloading your system with a massive spike in PGE2 that could potentially have deleterious consequences long term.Also, the results I got from oral castor oil were better than what I experienced with diligent PGE2 applications.Now, at the end of the day, this all still stems back to androgens causing this whole cascade of events.The whole process can be mitigated just by addressing the Testosterone and DHT at the beginning.But, obviously for people that aren’t willing to manipulate their hormone profile, or aren’t willing to implement certain things that they perceive as too experimental, things like castor oil can be excellent additions to a protocol.And for those who are willing to manipulate their hormones a bit more, or use higher risk treatment options, castor oil is still something I see as a potentially low risk addition to help solidify a strong, comprehensive regimen.Where Does Castor Oil Fit Into A Hair Loss Prevention Protocol?Something that will be asked is how oral castor oil compares to traditional treatment options.Castor oil operates via a totally different mechanism of action and cannot be compared to things like Finasteride, or Dutasteride, or RU58841, or even PGD2 inhibitors.The compound accomplishes what its meant to do, but it will not replace anti-androgens, or other compounds meant to do completely different things in the body.At the end of the day, a comprehensive protocol should address all factors, or address the root of the issue early enough in the cascade so sufficiently that nothing else matters.You can’t compare a PGE2 agonist to an anti-androgen, so keep that in mind.Where To Buy Food Grade Castor OilYou want to buy 100% castor oil, not Jamaican black castor oil.It’s clear and a pale yellow color.Food/Pharma grade (USP or BP) is ideal as it ensures a high enough standardization of Ricinoleic acid.Ricinoleic acid is the component of castor oil that boosts PGE2 and we care about.NOW Solutions Castor Oil is third party tested and meets our criteria for a high quality Castor Oil, and is also what I use personally.Related
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