Transcription
Looking for more ways to speed up injury repair with peptides? Well, let me introduce you to the Robin to BPC-157's Batman, and that is TB4 and TB500. But how do they work? What studies do we have on them? And when should you consider taking them? And how do they even compare to BPC 157? And if you do take them, what's the optimal dose, timing, and cycles? And can you take them orally? We're covering all of this and more in today's deep dive on TB4 and TB500. So, let's jump right in.
Starting with the mechanisms. Well, the first thing to understand when we're talking about the mechanisms and effects of TB4 and TB500 is that these two are not the same thing. Despite often being used interchangeably, TB500 is actually just a small segment of the larger peptide of TB4. So to understand TB500 first we have to understand that larger peptide TB4. So let's start there.
TB4 or thymosin beta 4 is a thymic peptide. Essentially all that means is it's a peptide that was originally derived from a mammal's thymus. And the thymus is an organ whose main responsibility is training the immune system, specifically T cells, to fight off invaders and to not fight your own tissue. Now, there are thymic peptides that are more specific to the thymus. Essentially, these ones are thymus hormones that act more specifically on immune system function. Think the alpha-thymosin peptides, such as thymosin alpha 1 or thymulin. But there are also the beta-thymosin peptides, aka TB4 and others. And these peptides, while they were still originally isolated from the thymus, are actually found in every single nucleated cell throughout the body. And this group of beta-thymosin peptides, also including TB10 and TB-15, all share the same main mechanism, which is cellular structure and cellular repair. And amongst all of the beta-thymosin peptides, TB4 is found in the highest quantities throughout the body. It also has the most research on it. Hence why it's the peptide you've probably heard of and what we're discussing for the rest of this video.
So why is TB4 so important for cellular structure and repair? Well, TB4 is a larger peptide. It's 43 amino acids long, and different segments of that amino acid chain are important for different functions. The most studied segment of that 43 amino acid sequence is amino acids 17 through 23, or the sequence LKKTEQ. This segment is responsible for binding G-actin, or the individual building blocks of actin. And actin is the protein that makes up the inner skeleton of every single cell and essentially allows that cell to maintain its proper structure and aids in the cell's ability to move. So by binding these individual building blocks of actin, TB4 essentially helps stabilize them and keeps them ready to use whenever the cell needs to build longer actin filaments to help the cell restructure or to help the cell move. And cells moving in this way is super important to aid in tissue repair and injury repair because these cells need to move to the site of injury in order to rebuild tissue there.
And in addition to this, cells moving in this way, building those actin filaments to help them move, is also super important for a process known as angiogenesis, which is another process super critical for tissue repair. And if you watched our video on BPC 157, you know all about angiogenesis because it is BPC 157's main mechanism to help with injury repair. But essentially, angiogenesis is just the creation of new blood vessel branches to help blood get to the site of injury. This is important because the site of injury is going to need oxygen and nutrients to help repair itself. And TB4's actin binding helps with the process of angiogenesis because it allows endothelial cells to move and create the lining of the new blood vessels that are forming. So you can probably start to see that this main actin-binding segment of TB4 is the main segment responsible for its ability to help with tissue repair and injury repair due to its ability to promote cell migration and angiogenesis.
Then, technically, TB500 is just that main actin-binding segment that we've been talking about, that seven amino acid segment out of the whole 43 amino acid segment that is TB4. And the idea was, "Oh, we're taking the main active part of TB4, just that seven amino acid sequence. So we should get all the same positive benefits of TB4, but it'll be cheaper and easier to produce, right?" Well, not so fast, because the issue with that logic is that TB4 has many other active sites outside of just the TB500 segment. So, if we're just using the small seven amino acid segment that is TB500, we might be missing out on other positive effects that TB4 has to offer. Namely, the first four amino acids of the 43 amino acid TB4 sequence are responsible for lowering inflammation and lowering scar tissue. And then the first 15 amino acid sequence of TB4 has been shown to be associated with increased cell survival and inhibiting apoptosis, or controlled cell death. And then there are even more mechanistic actions of TB4 that we don't know which part of the sequence they come from yet. For instance, TB4 has antimicrobial properties, and it also has the ability to activate additional genes or signaling pathways that are involved in the tissue healing process. So TB4's mechanisms are much, much wider scoping than just the actin binding that we get from that seven amino acid segment that is TB500.
And this distinction becomes crucial when looking at studies that look at the practical benefit of these two in animals or humans. And this is because TB4 has been far more extensively studied than TB500. And the results from these TB4 studies can't be directly translated to TB500 because TB500 is missing a lot of the mechanisms that TB4 has. So while TB500 still shares some of the benefits of TB4, results we see from the TB4 studies can't be translated one-to-one with TB500 because TB4 likely has a stronger effect than does TB500.
So let's walk through the research on the practical benefits of TB4 and TB500 based on all these mechanisms that we've talked about. So as we've alluded to, based primarily on the mechanism of the actin binding, but also due to TB4's anti-inflammatory effect and its ability to lower scar tissue production, TB4 and TB500's main benefit is tissue repair and injury healing. And the tissue that TB4 has been studied in the most is the skin and with superficial wounds. So specifically, in a phase 2 clinical trial of 73 humans, TB4 was found to accelerate wound healing by one month. And these wounds were chronic superficial wounds due to poor circulation. And additional human studies and additional studies in mouse models have further demonstrated this skin healing effect of TB4.
But to me, even more impressive is the TB4 research on improving heart tissue repair, especially after a heart attack. For instance, there was a study in mice that were having a heart attack that after the heart attack, TB4 was administered, and it improved multiple markers of heart structure and heart function, and it also improved mouse survival. And then in a small study in humans of 10 participants who had just had a heart attack, half of them were given stem cells that were pre-treated with TB4, and the other half were given just regular old stem cells. In the group that was given the TB4-treated stem cells, their heart function improved by 50% compared to the other group, and their walking distance improved by 14% compared to the other group.
The next tissue that we have evidence of TB4 being able to heal is the eye. And in a phase 3 clinical trial, again in humans, we had 18 participants who had diminished corneal sensation and a diminished ability for their cornea to heal due to a specific eye disorder. Half of these participants were given TB4 through drops, and TB4 caused 60% to have complete healing compared to only 13% in the placebo group. And in additional human studies, TB4 has been found to significantly improve symptoms of moderate to severe dry eye. And in additional studies in animal models, TB4 has been found to further improve cornea healing as well.
And then there's the area of healing that many of you watching this video are hoping to hear about, and that is musculoskeletal injury repair. Now, if you've watched our BPC 157 video, you know just how many studies there are on BPC healing all different sorts of injuries. For TB4, and especially for TB500, we don't have near as much of those type of studies. But we do still have some impressive studies that, along with that impressive mechanism of TB4, still make it promising for this use case. For instance, in one study in mice, one of the leg bones of the mice was fractured. And then one group of those mice was given TB4, the other placebo. The group given TB4 was found to have 25% stiffer bones and a bone that could withstand 41% higher forces before refraure. And then in another study looking at muscle repair in mice found that TB4 administration improved healing by two to three times compared to placebo. And impressively, this was in a dose-dependent manner. And while there are no direct studies on TB4 improving tendon or ligament healing, based on these studies and the mechanism, it would make sense that TB4 would have some promise there as well.
But the studied effects of TB4 don't stop at healing all these tissues we've just talked about. Because TB4 also has studied effects in the brain. And these positive neurologic effects stem not only from the mechanisms we've already talked about but also due to some more direct action in brain cells, such as TB4's ability to remodel blood vessels in the brain and promote neuron growth and just protect brain cells from damage. And through these mechanisms, there have been multiple studies in which TB4 has been given to mice after these mice were made to have a stroke. And this resulted in the mice that were given the TB4 having significantly better functional outcomes after their strokes. Similarly, there are also studies in mice who were made to have a traumatic brain injury. These mice were then given TB4 in the days after, and it significantly, again, improved functional outcomes and decreased long-term brain damage.
So overall, TB4, and by proxy possibly TB500, have a ton of potentially super promising use cases based on all those mechanisms we talked about. But just like BPC 157, we have to talk about how those same mechanisms could also pose a safety risk. But to start the safety discussion off, let's talk about the positives on the safety front for TB4 and TB500. So just like we talked about for BPC, peptides in general have a lot going for them safety-wise. First of all, they're rapidly metabolized and excreted by the liver and the kidneys, which allows them to not build up and accumulate in the body as many drugs do. Peptides also often have specific sites of action, which limit their off-site negative consequences that could occur. And finally, peptide metabolites are just amino acids, so they're non-toxic, which is not the case for many drugs and supplements.
And then for TB4 specifically, we have multiple short-term animal studies in which high, high doses of TB4 were used, and there was no reported adverse events or toxicities. And even in a more long-term study in mice that they administered TB4 two times per week for six months, there was no adverse outcomes at all reported. And then impressively, we even have some human safety data. In a phase one clinical trial, they gave 10 participants very large doses of TB4 IV. We're talking up to 260 mg per day for 14 days, and no adverse outcomes or toxicities were reported. And when used topically daily for three months in human trials of 70-plus participants for those skin wounds we talked about earlier, again, there were no adverse events or toxicities reported. So comparably to BPC 157, for instance, we have better human safety data.
But we're still not in the clear on this one yet. Reason being is, as we'll discuss later, most people are not using TB4 IV for only 14 days or only using it topically. And we also do not yet have long-term data after people take a course of TB4 or TB500. So to actually prove that it's safe, we would need human studies that have the humans actually taking TB4 like people are taking it in real life. And we would need long-term data on the adverse effects of taking this type of TB4 course. So until we get that data, it's important to speculate on the potential safety risks of taking TB4.
And while there could be potential short-term side effects of taking TB4 or TB500, the one main real theoretical risk that comes with taking TB4 or TB500, in my opinion, is the potential to promote cancer, which, if you've watched that BPC video, is the same concern I have with that. And ironically, this potential risk of TB4 comes from the same mechanisms that make it so promising for tissue healing. The first of which, like we talked about in that BPC video, is TB4's ability to promote angiogenesis. While TB4 is less pro-angiogenic compared to BPC 157, it's still important to consider that that increased angiogenesis from TB4 could be helping promote a cancer. And the mechanism here is essentially that as a tumor grows and divides, it needs to get more nutrients and oxygen to the edge of that tumor so it can continue to grow and divide. And how it gets those nutrients there is to promote more blood vessels to the edge of the tumor, thus increasing angiogenesis to grow the tumor. So by upregulating angiogenesis through that actin binding, like we talked about, TB4 and TB500 could be potentially promoting the growth of a cancer that's already there.
However, again, the risk of TB4 or TB500 promoting cancer is not just due to increasing angiogenesis. For instance, TB4's ability to promote cell migration through that actin binding has also been linked to tumor progression in studies. Specifically, TB4 has been found to promote something known as the epithelial-mesenchymal transition, which essentially just allows cells to move out of their initial position and become more mobile. This is a super important process for cancers to become more invasive and to metastasize. And then furthermore, the ability of that first 15 amino acid sequence of TB4 to decrease apoptosis, or decrease controlled cell death, could also promote cancer growth because in cancer, we want these cells to die off. So essentially, TB4 could be promoting prolonged cancer cell survival through this ability to decrease apoptosis. And finally, a mechanism we actually haven't talked about yet. TB4 has other amino acid segments that are used to inhibit a process known as ferroptosis. And ferroptosis is essentially the killing off of cells due to a high iron load and high oxidative stress. And studies have demonstrated that TB4 could further promote cancer growth through inhibiting this ferroptosis and essentially allowing the cancer cells to survive and not die off due to this high oxidative stress and iron load. So all to say, there are multiple ways in which TB4 overexpression has been demonstrated to potentially promote cancer in these basic science studies. So although we have no evidence of TB4 promoting cancer in animals or humans when it's used in the studies that we've talked about, I think that all of these mechanisms do warrant a pretty careful risk-benefit analysis if you're thinking about taking TB4 or TB500.
And the start of this discussion sounds pretty similar to the one we had for BPC 157, which also has some theoretical cancer risk. And essentially, my recommendation is this: If you are someone who has active cancer, or who has ever had cancer in the past, or has even had a precancerous diagnosis in the past, such as a precancerous colon polyp, or if you are someone who has a strong family history of cancer, if you fall into any of these groups, I would avoid TB4 and TB500 altogether. And even if you don't fall into that group, if you are considering taking TB4 or TB500, until I see some real safety data, I would definitely recommend that you are properly screened for cancer prior to starting TB4 or TB500. That means being up to date on your colonoscopy, your PSA and DRE if you're a male, and your mammogram and Pap smear if you're a female, and also being up to date on your chest CT if you're a prior smoker, and your skin checks if you have a strong risk of skin cancer. And even then, once you are actively screened, you have no active cancer or history of cancer or family history, I still wouldn't be just taking TB4 or TB500 indefinitely or just taking it for preventative purposes. There's obviously no way to continuously check for cancer or even intermittently check for cancers with 100% certainty. So, the risks to me definitely outweigh the benefits for long-term continuous use.
But under what scenarios do the benefits actually outweigh the risks, and you actually should consider taking TB4, TB500? And if you are going to, should you take TB4 or TB500, or should you just disregard them both and take BPC 157 instead? Well, to start off answering these questions, it's worth noting that again, TB4 and TB500 are not currently FDA approved for human use. So, I'm really not recommending anyone take them currently. But if you are considering taking it still, it's best to do so with caution and with your doctor's advice. But let's go over my general recommendations here for those of you who, again, are cancer-free and have been properly screened for cancer.
First, on the TB4 versus TB500 front, to me, I'm going with TB4 here almost every time. Reason being is that mechanistically, TB4 has way more potential benefits than just the actin binding domain. And that's all TB500 has. And almost all studies that demonstrate tissue healing benefit in both humans and animals use TB4, not TB500. So, we don't really have that much evidence to say that TB500 is even beneficial at all without the extra segments that TB4 has. And while TB4 could carry some additional cancer risk due to these extra segments, like we talked about earlier, the main cancer risk is still coming from that actin-binding segment, which TB500 obviously still has. So, as long as you are using them short-term in the correct situation, to me, I think the extra risks of TB4 are outweighed definitely by the extra benefits of TB4. And I would definitely go that direction rather than TB500.
But when should you consider taking TB4? And then the other important part of this discussion is when should you consider taking it with BPC 157, or just using one or the other? These two are the most important and probably most well-known tissue healing peptides. And if you've watched both of our videos so far, you can probably pick up on the fact that they can definitely work synergistically together due to the fact that both of them work on different key mechanisms of the tissue repair process. TB4, on one hand, is working more on cellular structure and repair through that actin-binding domain mainly, but having, again, other mechanisms as well. On the other hand, BPC 157 is more focused on improving angiogenesis, but through increasing nitric oxide and VEGF, which are different and more potent than TB4's way of increasing angiogenesis. So, combining the two different mechanisms could definitely theoretically be beneficial in certain types of injury repair.
So, let's walk through when I'd consider using both, or when I'd consider using just one or the other. Well, for TB4, the best human evidence, as we've discussed, is using this topically for superficial wounds, such as skin ulcers, cuts, abrasions, etc. And there's also pretty great human evidence for using it for eye conditions as well. So, given the fact that we have human evidence in these use cases, and topical use brings about less cancer risk, these are pretty great, although less common use cases of TB4. And given that we have much more evidence in these use cases than we do for BPC 157, I'd definitely be starting with TB4 here and then adding in BPC 157 if you're not getting enough effect or if it's a pretty significant wound. And on a similar note, I would be using TB4 before BPC 157 when it comes to repairing the heart after a heart attack, for instance. TB4 has some human data that BPC 157 does not have in this arena. So, I'd be using that one first. But because BPC 157 could act synergistically here, realistically, I'd probably be using both together for a short course after a heart attack. Although again, definitely doing this in conjunction with your doctor, and I'm not really recommending anyone do this right now.
And then that leaves us with the most common use case of TB4 and BPC 157, and that is musculoskeletal injury repair. Which way should you go here? Well, to me, here, BPC 157 wins hands down. While we don't have true human data for either, BPC 157's data in mouse models far exceeds the same data we have for TB4. There are way more studies on BPC 157 healing a wide variety of musculoskeletal injuries. And the studies that we do have are just far more impressive in regards to BPC 157's healing effect compared to TB4's. And then even on top of that, I believe that there's more mechanisms and reasons to say that TB4 might promote cancer risk than BPC 157 would. So to me, I think TB4 might be slightly more risky even than BPC 157. So because of this, if both were legal, I'd recommend starting with just BPC 157 alone for almost all chronic injuries, meaning all chronic tendon, ligament issues, muscle strains, etc. And then if healing plateaus and you just still aren't getting all the way there, you could add a short course of TB4 alongside the BPC 157. I personally wouldn't start with both as generally for these more mild chronic injuries, BPC 157 is sufficient, and I just don't like to incur more risk than we need to. So one potentially cancer-promoting compound is better than two.
Now, in contrast, if you have a new acute injury, that's when I would consider taking both BPC 157 and TB4 together right off the bat. TB4 can be especially beneficial in the initial phases of the healing process, as it's one of the signals the body uses to start the repair process. So if you have a major injury or are recovering post-surgery, doing TB4 and BPC 157 in combination right from the start could be a good idea. However, for more minor strains and tweaks, I'm not normally doing both. I'm normally just sticking with just BPC 157 as it will likely be sufficient. But in truth, I'm normally staying away from both of these peptides because I think the risks just outweigh the benefits when the injury is very minor and it can heal using other methods.
And this whole discussion we just had on musculoskeletal injuries also applies to brain injuries as well, such as traumatic brain injuries or strokes. So I prefer BPC 157 alone for minor injuries, such as a mild concussion. Although similarly, I don't necessarily recommend this for minor cases, just given the risk-to-benefit ratio. But for strokes or more significant traumatic brain injuries, doing BPC 157 and TB4 together from the start could be a good idea. So if it were legal for human use, those would be your TB4 use cases in my opinion: One, superficial skin wounds in certain eye conditions. Two, following a heart attack, stroke, or traumatic brain injury. Three, in stubborn chronic musculoskeletal injuries that are not responding to BPC 157 alone. And four, in acute, more major musculoskeletal injuries using TB4 and BPC 157 in combination right away.
But for these use cases, what form, dose, timing, and cycles would hypothetically be the best? In regards to forms, for superficial skin and eye wounds, a topical form is used in all the human studies we've mentioned. So for those skin wounds, they applied a 0.3% TB4 gel to the area one time per day for up to three months. And then for the eye issues, they used a 0.1% TB4 eye solution, which they applied to the affected eyes four to six times per day for up to 28 days. Given that these are superficial issues, I think a topical form obviously makes sense, and that is what was used in these human studies. And because we have human studies demonstrating efficacy at this dosing pattern, that's exactly what I would stick with for skin or eye issues.
So for the rest of this video, we're talking about the form, dose, timing, and cycles specifically for musculoskeletal injuries, as well as for cardiac and neurologic injury, which are similar in the dosing and everything else required to musculoskeletal injuries. For the form of TB4 for these injuries, I would obviously stay away from topical administration, as it's just not going to penetrate deep enough to help the repair of these deeper tissues. But what about an oral form? Well, unfortunately, TB4 is not like the acid-resistant BPC 157, which has animal studies demonstrating efficacy with oral administration. TB4, on the other hand, is just like most other peptides that are really not bioavailable orally. And the reason for this is that peptides in general are very easily degraded by the acid in the stomach or other enzymes in the digestive tract. And even then, they're not very well absorbed. And based on its structure and mechanism, TB4 likely fits the mold of the general peptide that is not bioavailable orally. Which is why, to my knowledge, there is not a single study in animals or humans using oral TB4. So because of this, despite there being oral TB4 forms available, I would 100% stay away from these oral forms until we actually get an advanced formulation of it that will allow us to have a studied benefit of oral TB4.
So, if we're staying away from both oral and topical TB4 administration for these injuries, that basically leaves us with IV or subcutaneous/intramuscular. All of which are, per the FDA, not for human use currently. So again, the rest of our discussion here is purely educational and hypothetical. And while the only human studies we have on these forms are the IV safety studies in humans that we mentioned, IV use is really not practical for the everyday user. So really for musculoskeletal or cardiac or neurologic injuries, you're really sticking with the subcutaneous form of TB4 here, which I prefer over intramuscular administration just for safety purposes, and you're likely going to get a very similar effect.
But what about the hypothetical dose of these subQ injections? Well, I'll say off the top that this one is really tricky for musculoskeletal injuries, as the evidence even in animal models is very sparse compared to BPC 157, which has a ton of animal studies, and anecdotally, people are doing all sorts of different things for TB4 dosing. But let's parse through the data to give you the best evidence-informed estimate on the optimal dose. So just like our BPC video, let's start with the human equivalent dose to the mouse studies that were injecting TB4 systemically. So while we don't have a ton of studies in this category, the studies we do have, including that mouse fracture study that we talked about, used 6 mg per kg intraperitoneally. So calculating the human equivalent dose of this gives us 4.9 mg per kg for humans. But since this was an intraperitoneal injection, or an injection straight into the abdominal cavity in these mice, we have to further adjust our dose because intraperitoneal dosing has about a 40% higher bioavailability than subQ. So after we adjust for that, that gives us a human equivalent dose of about 6.9 mg per kg. So for an average 70 kg adult, that would be 48.3 mg per day, which, if you've looked into peptide pricing at all or heard about anecdotal use, that is much higher than what people are really using, and it would be way too expensive for most to afford. So we have to look at additional data points as well.
And the two studies that are the most helpful to look at here are the human studies that used IV TB4. First is the study we've already mentioned that dosed up to 260 mg per day for 14 days and found no adverse effects. But that's only one study, and the participants weren't followed after that 14-day period at all. Second, then we have another human study dosing up to 5 micrograms per kilogram IV every day for 10 days and then following up for 28 days, which definitely increases the legitimacy of that safety data. And this study also found no adverse effects. So now we have two human studies demonstrating that at doses of 5 micrograms per kilogram IV and lower, we have no adverse effects. Thus, in an attempt to get as close to that human equivalent dose from the mouse study that was efficacious, while also using a dose that is affordable and practical for human use, and most importantly, using a dose that we have the most safety data on, I would say starting at 5 micrograms per kilogram IV would be our way to go.
So to translate that IV dose to a subcutaneous dose that humans are going to be more able to take, we can assume that subcutaneous administration has about 70% bioavailability compared to the 100% of the IV. So if you account for this, you then get a dose of 7.14 micrograms per kilogram per day. So for an average 70 kg adult, that would be about 500 micrograms per day of TB4 subcutaneously. And you may notice that I keep saying daily dosing or per day. And that's because I definitely think that TB4 should be administered at least once per day. And reason for this is, first off, most of the animal studies doing injectable TB4 were doing once daily dosing. And mechanistically, this also makes sense because TB4 has a pretty short half-life, with studies noting its half-life to be about only 1.5 hours. But you might notice that this strays from a lot of the anecdotal advice you hear about TB4 or TB500. The reason for this is that TB500 actually has a longer half-life, with metabolites being detected for up to 72 hours after administration. So if you're taking TB500, then great, two to three times weekly dosing might be optimal. But if you were taking TB4, the superior one, like we've talked about, then doing it daily is going to be better to give you more consistent plasma levels and consistent tissue exposure, which is important for optimal tissue healing.
So in sum, hypothetically, based on the very limited data we have, I think that 500 micrograms per day is the best starting point. Then, given the other human safety data we have, if after a week or two you have no negative effects, but you're also not noticing the healing effects that you want, increasing your dose to even 1 milligram could be okay. But of course, this isn't medical advice. You're doing this in conjunction with your doctor. And again, you're not really doing this at all right now because it's not FDA approved for human use.
But theoretically, if you were taking T4 in this way, when in the day should you take it, and for how many days, weeks, or months? Well, in regards to daily timing, there are really no head-to-head studies looking at once versus twice daily dosing or using the TB4 at night versus the morning. So, the timing discussion here is purely speculative, just based on the mechanisms. So, for morning versus nighttime dosing for TB4, it's far, far less important than for a hormonally related peptide, i.e., a GnRH agonist, in which circadian rhythm and hormonal pulsing matters a great deal. That being said, it could make some theoretical sense that you might get a marginal benefit if you took your TB4 at night compared to the morning, as the circadian rhythm slightly upregulates tissue repair mechanisms at night.
Then, in regards to how many times during the day should you administer TB4, all the animal studies and the human IV studies we've mentioned use just once daily dosing. So because of this and because of just practicality, I think starting at once daily dosing for TB4 is probably sufficient. But if you are increasing your dose from there, I think it could make sense to start doing twice a day dosing, aka maybe doing 500 micrograms in the morning and 500 micrograms at night. Given the very short half-life of TB4, this twice daily dosing could improve plasma and tissue levels throughout the day. Hence why I think it could be beneficial over the once a day dosing if you are increasing your dose. And if you're already using BPC 157 twice daily, aligning your TB4 to that schedule could also make sense as well.
And finally, how long should you be using TB4 in this manner? Well, similar to our discussion with BPC, the duration is very difficult to determine based on studies. There's no human equivalent duration like there is a human equivalent dose. So, determining the duration of a cycle is even more challenging than the dose or the frequency. And it's going to be purely speculative based on, again, mechanisms, safety concerns, and really just anecdotal evidence. But based on all that, I like a four to six week on cycle for TB4 and then cycling off for at least six weeks prior to using it again if you were going to. This helps give you the benefits that you might get from it while also mitigating long-term risk, especially that cancer risk. I like a slightly shorter cycle here compared to BPC 157, given the fact that again, I do think TB4 has slightly more cancer risk compared to BPC 157. And again, similar to BPC, I don't like the idea of just continually cycling on and off this one. Again, this is meant for targeted use only. And once your injury heals, then it's time to stop using it. And even if it hasn't healed after a couple cycles, then it might be time to be looking for different therapies, which again, I'm doing right now anyways until this one is legal in humans. And finally, it's also important to mention here that you can likely do this one every day rather than doing the five-day on, two-day off cycle like you would for a hormonally related peptide like GnRH agonist. The five-day on, two-day off thing is to avoid desensitization and receptor downregulation, which is important for, again, hormonally related peptides, but you have less of a concern with that for TB4 mechanistically. So everyday dosing will do for this cycle.
Compounding pharmacies cannot legally produce TB4 right now. And yes, I'm aware that some still do, but truthfully, if a compounding pharmacy isn't following the regulations in this way, then I really just can't trust they're following other quality control measures as well. So, I generally stay away from these compounding pharmacies, and I'm not recommending TB4 right now until it can be legally compounded again. That being said, these pharmacies that are still producing TB4 are still safer than the research use-only peptides you get online. And that's a pretty important distinction to again make. A legitimate, state-regulated compounding pharmacy is held to a much, much higher standard for sterility, quality, purity, etc., compared to these research use-only online peptides, which have no regulation whatsoever. So I would not go that route. But because I do know some of you are still going to do it, I would love for it to be as safe as possible. So we'll touch on that briefly. We talk about this in more depth in the BPC video, but in brief here, you need the following tests and the results of those tests readily available if you want your peptide to be as safe as possible.
The first test you need is identification and purity testing, both an HPLC and a mass spec, which is essentially proving that you are getting what you think you are getting. And for TB4 and TB500, this is incredibly important because many companies are marketing TB4 as TB500, even though, again, technically TB500 is just that small segment within TB4. So you want to make sure if you're following my advice that you're getting TB4, the whole 43 amino acid sequence. So you really want to check that amino acid sequence that is listed. Then the second test that you need is a USP 85 endotoxin test. This is the industry standard to test for endotoxins, or essentially these bacterial products that can produce pretty severe immune reactions. And then finally, you want a USP 71 sterility test as well, which again is the industry standard test, but this time for sterility, making sure that there's no bacteria, virus, or any other microorganism within that vial, which can happen if it's compounded non-sterily. If you have all of those tests and they all check out, that would be the safest you could get from a research use-only peptide source. But again, I'd stay away, really.
If you haven't watched the BPC 157 video yet, check that out here. Then subscribe for more peptide videos coming soon. And if you've already done both of those things, check out this video on sauna use to see how that could also aid in your recovery and your longevity.