akn
Musclechemistry Member
by Mike Arnold
With insulin now popular among all levels of bodybuilders, the demand for information has grown exponentially, especially over the last 5 or so years. This has led to a variety of articles being published addressing everything from insulin-based nutrition, injection timing, frequency of use, insulin sensitivity/resistance, and many other topics to numerous to mention here. Information that used to be considered cutting-edge is now fundamental, as methods of use continue to evolve.
Unlike steroids, bodybuilders have traditionally trailed the medical community in terms of overall insulin knowledge; not necessarily in the area of stimulating muscle growth, but in how this hormone affects the body as a whole. This is particularly true when it comes to the different insulin analogues. With diabetes being a societal epidemic, we would expect this to be so, but there is no need for us to be ignorant on the subject. To this end, I decided to put together a brief overview of these analogues, touching on the pros and cons of each one. Hopefully, this will allow you to more easily determine which type of insulin is best for you and how to properly implement them within your program.
The most commonly used and familiar form of insulin among bodybuilders is regular human insulin, known by the brands names Humulin R and Novolin R and made by Eli Lilly and Novo Nordisk, respectively. Considered by most to be the best form of insulin for beginners, RHI (short for regular human insulin) is the exact same kind of insulin produced by your body, except that it is synthesized in a lab rather than your own pancreas.
Despite being perhaps less glamorous than the engineered analogues, RHI is still the best form of insulin for the largest majority of people. There are several reasons for this. For one, it has a lower risk of hypoglycemia compared to the faster-acting versions, making it a safer choice for the less experienced. With potentially drastic differences in insulin sensitivity among individuals, and the fact that newer users are still learning how their body responds to this hormone, this is a significant benefit.
With a peak activity of about 4-5 hours (it hangs around a little while after that, but most of it has been absorbed into the bloodstream by that point), a single injection is capable of stimulating glycogen and protein synthesis to a significant degree. Furthermore, so long as it is not over-used, the risk of developing insulin resistance is minimal (this is especially true when combined with preventative supplementation). Technically, one could say this about any form of insulin, but RHI can be used 4-5 days per week, indefinitely, while still being able to make this claim—something that can’t be said for every analogue. Not only does this provide substantial benefit in terms of recovery and growth, but it allows one to avoid the yo-yo effect (get big, shrink down, get big, shrink down, etc) associated with the more intensive programs that require an ON/Off approach.
In my opinion, RHI is the ideal training-based insulin for off-season use, as a single pre-workout injection will remain active throughout the entire training window, which ranges from the start of training until a couple hours afterward. While pre-training is the single most beneficial time to use insulin, the risk of hypoglycemia is greater in comparison to most other times of the day, so beginners will generally be better off starting with the post-workout method before graduating to pre-workout use.
The majority of individuals will never need to move beyond this type of program. This is a less a reflection on the bodybuilders level of development as it is one’s belief system, as many bodybuilders think that the cons begin to outweigh the pros when using insulin more frequently than this. For these individuals, RHI is usually the preferred choice.
Regular human insulin is supposedly less mitogenic than several other forms of insulin, meaning its ability to initiate mitosis (the splitting of mitotic cells) is less pronounced. While this is mostly irrelevant in the face of good health, there is evidence to suggest that it can cause cancer cells to proliferate at a faster rate, as cancer cells are highly mitotic. This has caused some researchers to disparage the long-term use of certain insulin analogues in diabetics, while others reject the idea together, claiming that all insulins are equally safe in this regard. Note: Before one starts thinking they can use the more mitogenic forms of insulin (which we will get to later) to speed up muscle cell hyperplasia, think again, as muscle cells are not mitotic.
The 2nd most commonly used types of insulin are the fast-acting versions, such as Humalog (insulin lispro), Novolog (insulin aspart), and Apidra (insulin glulisine). All of these insulins have a very rapid release rate, hitting the bloodstream within 10-30 minutes of administration and possessing a peak activity of about 2-3 hours. There are several advantages to the rapid-acting insulins over the slower-acting forms, a few of which are directly connected to their short active lives within the body.
The first of these is their reduced effect on insulin sensitivity/metabolic health. With such a short duration of action, total exposure time is significantly reduced in comparison to other forms of insulin (when administered at an equal frequency). With length of exposure (and total weekly dose) being one of the most important factors in determining how likely we are to develop insulin resistance, it only makes sense that the fact-acting insulins are the least likely to cause problems in this area.
While fat loss can be avoided with all insulins, the rapid-acting versions are also the least likely to interfere with fat metabolism. Not only does insulin have a strong anti-lipolytic effect (prevents fat cells from releasing fatty acids into the bloodstream) on adipose tissue, but it simultaneously stimulates glucose uptake into the fat cell. Therefore, the longer insulin remains active, the more difficult it becomes to lose body fat/stay lean.
This is part of the reason why consuming the majority of our carbs around training is less likely to lead to fat gain—because insulin concentrations are only elevated for a limited period of time, rather than all day long. Understandably, this makes the faster-acting insulins preferable when prioritizing fat loss, such as during pre-contest preparation.
However, their fast-acting nature is also what makes them the most dangerous. With such a rapid release rate into the bloodstream, blood glucose levels drop much more quickly than with other insulins, putting the user at greater risk for experiencing a hypoglycemic event. Unless one is either is instructed by a competent coach or personally monitored for signs of hypoglycemia, the fact-acting analogues are not a good choice for beginners.
One seldom mentioned variable between the different insulins is their affinity for the insulin and IGF-1 receptors. A drug’s “affinity” refers to the strength with which a ligand (drug, hormone, neurotransmitter, etc) attaches to a receptor site. Binding affinity, along with efficacy, are the two factors responsible in determining a drug’s potency. Therefore, the greater a drug’s binding affinity, the greater its potency.
Since insulin and IGF-1 have the ability to share receptors, they each have their own binding affinity for the insulin and the IGF-1 receptor. Obviously, with both of these hormones playing a critical role in the muscle growth process, the greater their affinity for these receptors, the greater their muscle building potential. Since regular human insulin is the benchmark for comparison, let’s look at how all three fast-acting insulins stack-up against it.
Of the three, Apidra (insulin glulisine) is the weakest, possessing a slightly weaker binding affinity for the insulin receptor than RHI. However, its binding affinity for the IGF-1 receptor is a full 4-5X weaker. Humalog (insulin lispro) is closer to RHI, with an insulin receptor binding affinity just under RHI, and an IGF-1 binding affinity about 1.5X higher. Novolog (insulin aspart) is the strongest of the bunch, with an insulin receptor binding affinity similar to Humalog, but an IGF binding affinity 4-5X higher than regular human insulin. This makes Novolog the most potent of the fast-acting insulins, but also the most mitogenic.
The next insulin on the list is NPH (neutral protamine hagedorn), also known as Humulin N/Novolin N. I am not going to spend much time on this intermediate-acting insulin, simply because I see no need to. I think it’s a poor choice for bodybuilders for several reasons. First of all, it’s the least consistent in terms of absorption rates. With an onset time of 1-4 hours and duration of action ranging from 9 to 16 hours it’s just too unpredictable for bodybuilders, who tend to time their insulin use according to their food intake. Furthermore, if one is looking for a sustained elevation of insulin levels, why not just use the longer-acting insulins, such as Lantus or Levemir, both of which provide all the benefits of NPH, but with a much more consistent release rate.
I don’t consider mixed insulin preparations to be any better. Mixed insulin products are those which combine more than one type of insulin in the same vial. Although these can be useful for diabetics, non-diabetic bodybuilders do not require this type of layered release in order to properly manage blood glucose levels. If you are contemplating insulin use, you are better of choosing something else.
Finally, we come to the long-acting insulins—Lantus (insulin glargine) and Levemir (insulin detemir). First off, I want to say that despite being the least likely to cause hypoglycemia I don’t consider them appropriate for beginners, and as with all newer drugs, we are still learning how to best use them. Even in my own coaching practice, my opinions regarding their optimal application have changed dramatically within just the last 6 months. More than any other form of insulin, these are the most likely to cause insulin resistance, especially at higher dosages. This makes frequent, long-term use a bad idea. Furthermore, if used inappropriately, fat gain is likely.
Between the two, Lantus has a longer duration of action (about 24 hours) and a more even release rate, with little to no discernible peak. On the other hand, Levemir stays active for 12-24 hours, depending on dose, but that isn’t the only difference between the two. When it comes to IGF-1 binding, these two drugs are at the opposite ends of the spectrum. In short, Lantus is an IGF-1 powerhouse. With a binding affinity 6-8X that of RHI (some studies have shown it to be up to 500X higher, although this is certainly incorrect), it exceeds all other insulins in this regard.
When it comes to its effect on IGF-1 levels, research has shown it to be the only insulin capable of elevating IGF-1 levels beyond what is seen with regular human insulin. The most likely mechanism for this is the absence of IGF-1-like activity at the pituitary. This, combined with its impressive binding affinity, should technically make Lantus the most anabolic form of insulin available. This doesn’t necessarily mean it’s the best (what is “best” can change from person to person), but in my experience, it can be helpful for breaking past plateaus. So long as it is used properly, insulin sensitivity can be maintained.
If Lantus is the most anabolic insulin, then Levemir is the least. With an insulin and IGF-1 receptor binding affinity weaker than that of regular human insulin, it is low man on the totem pole. Of course, it will still perform all the physiological functions normally associated with insulin, but with a comparatively reduced, overall anabolic effect. From a bodybuilding standpoint, there are no known advantages to using Levemir over Lantus, but from a harm reduction standpoint, it is yet to be determined.
One concern among researchers is Lantus’s exaggerated mitogenic potency, which is directly connected to its greater IGF-1 binding/production. As mentioned earlier, the greater insulin’s mitogenic potency, the more likely it is to induce cell division in mitotic cells, such as cancer cells. While this will not cause cancer, it could be a big problem for someone who already has cancer, causing it to grow at an accelerated rate and/or metastasize. Several studies have been conducted with conflicting results (recent studies have shown no negative effects in this area).
Although this might sound scary, when one looks at the bigger picture, it becomes apparent that it is really only a minor concern. Not only do bodybuilders use Lantus much less frequently than diabetics (if they’re smart), but a drug like growth hormone, which directly increases IGF-1 levels to a far greater degree than insulin (especially at bodybuilder doses), is a significantly greater risk factor. Yet, bodybuilders routinely engage in its use without even the slightest concern for its effect on cell division. Therefore, it seems kind of silly to place our attention on Lantus when other PED’s are much more likely to have a negative effect in this area.
With so many different types of insulin available on today’s market, trying to determine which one is best can be a difficult task for many bodybuilders. When used properly, the benefits on recovery and growth are substantial and side effects minimal. On the other hand, improper use is likely to lead to metabolic dysfunction and eventually, damage to one’s physique. Hopefully, the information presented herein will help eliminate some of the initial confusion and point you in the right direction.
With insulin now popular among all levels of bodybuilders, the demand for information has grown exponentially, especially over the last 5 or so years. This has led to a variety of articles being published addressing everything from insulin-based nutrition, injection timing, frequency of use, insulin sensitivity/resistance, and many other topics to numerous to mention here. Information that used to be considered cutting-edge is now fundamental, as methods of use continue to evolve.
Unlike steroids, bodybuilders have traditionally trailed the medical community in terms of overall insulin knowledge; not necessarily in the area of stimulating muscle growth, but in how this hormone affects the body as a whole. This is particularly true when it comes to the different insulin analogues. With diabetes being a societal epidemic, we would expect this to be so, but there is no need for us to be ignorant on the subject. To this end, I decided to put together a brief overview of these analogues, touching on the pros and cons of each one. Hopefully, this will allow you to more easily determine which type of insulin is best for you and how to properly implement them within your program.
The most commonly used and familiar form of insulin among bodybuilders is regular human insulin, known by the brands names Humulin R and Novolin R and made by Eli Lilly and Novo Nordisk, respectively. Considered by most to be the best form of insulin for beginners, RHI (short for regular human insulin) is the exact same kind of insulin produced by your body, except that it is synthesized in a lab rather than your own pancreas.
Despite being perhaps less glamorous than the engineered analogues, RHI is still the best form of insulin for the largest majority of people. There are several reasons for this. For one, it has a lower risk of hypoglycemia compared to the faster-acting versions, making it a safer choice for the less experienced. With potentially drastic differences in insulin sensitivity among individuals, and the fact that newer users are still learning how their body responds to this hormone, this is a significant benefit.
With a peak activity of about 4-5 hours (it hangs around a little while after that, but most of it has been absorbed into the bloodstream by that point), a single injection is capable of stimulating glycogen and protein synthesis to a significant degree. Furthermore, so long as it is not over-used, the risk of developing insulin resistance is minimal (this is especially true when combined with preventative supplementation). Technically, one could say this about any form of insulin, but RHI can be used 4-5 days per week, indefinitely, while still being able to make this claim—something that can’t be said for every analogue. Not only does this provide substantial benefit in terms of recovery and growth, but it allows one to avoid the yo-yo effect (get big, shrink down, get big, shrink down, etc) associated with the more intensive programs that require an ON/Off approach.
In my opinion, RHI is the ideal training-based insulin for off-season use, as a single pre-workout injection will remain active throughout the entire training window, which ranges from the start of training until a couple hours afterward. While pre-training is the single most beneficial time to use insulin, the risk of hypoglycemia is greater in comparison to most other times of the day, so beginners will generally be better off starting with the post-workout method before graduating to pre-workout use.
The majority of individuals will never need to move beyond this type of program. This is a less a reflection on the bodybuilders level of development as it is one’s belief system, as many bodybuilders think that the cons begin to outweigh the pros when using insulin more frequently than this. For these individuals, RHI is usually the preferred choice.
Regular human insulin is supposedly less mitogenic than several other forms of insulin, meaning its ability to initiate mitosis (the splitting of mitotic cells) is less pronounced. While this is mostly irrelevant in the face of good health, there is evidence to suggest that it can cause cancer cells to proliferate at a faster rate, as cancer cells are highly mitotic. This has caused some researchers to disparage the long-term use of certain insulin analogues in diabetics, while others reject the idea together, claiming that all insulins are equally safe in this regard. Note: Before one starts thinking they can use the more mitogenic forms of insulin (which we will get to later) to speed up muscle cell hyperplasia, think again, as muscle cells are not mitotic.
The 2nd most commonly used types of insulin are the fast-acting versions, such as Humalog (insulin lispro), Novolog (insulin aspart), and Apidra (insulin glulisine). All of these insulins have a very rapid release rate, hitting the bloodstream within 10-30 minutes of administration and possessing a peak activity of about 2-3 hours. There are several advantages to the rapid-acting insulins over the slower-acting forms, a few of which are directly connected to their short active lives within the body.
The first of these is their reduced effect on insulin sensitivity/metabolic health. With such a short duration of action, total exposure time is significantly reduced in comparison to other forms of insulin (when administered at an equal frequency). With length of exposure (and total weekly dose) being one of the most important factors in determining how likely we are to develop insulin resistance, it only makes sense that the fact-acting insulins are the least likely to cause problems in this area.
While fat loss can be avoided with all insulins, the rapid-acting versions are also the least likely to interfere with fat metabolism. Not only does insulin have a strong anti-lipolytic effect (prevents fat cells from releasing fatty acids into the bloodstream) on adipose tissue, but it simultaneously stimulates glucose uptake into the fat cell. Therefore, the longer insulin remains active, the more difficult it becomes to lose body fat/stay lean.
This is part of the reason why consuming the majority of our carbs around training is less likely to lead to fat gain—because insulin concentrations are only elevated for a limited period of time, rather than all day long. Understandably, this makes the faster-acting insulins preferable when prioritizing fat loss, such as during pre-contest preparation.
However, their fast-acting nature is also what makes them the most dangerous. With such a rapid release rate into the bloodstream, blood glucose levels drop much more quickly than with other insulins, putting the user at greater risk for experiencing a hypoglycemic event. Unless one is either is instructed by a competent coach or personally monitored for signs of hypoglycemia, the fact-acting analogues are not a good choice for beginners.
One seldom mentioned variable between the different insulins is their affinity for the insulin and IGF-1 receptors. A drug’s “affinity” refers to the strength with which a ligand (drug, hormone, neurotransmitter, etc) attaches to a receptor site. Binding affinity, along with efficacy, are the two factors responsible in determining a drug’s potency. Therefore, the greater a drug’s binding affinity, the greater its potency.
Since insulin and IGF-1 have the ability to share receptors, they each have their own binding affinity for the insulin and the IGF-1 receptor. Obviously, with both of these hormones playing a critical role in the muscle growth process, the greater their affinity for these receptors, the greater their muscle building potential. Since regular human insulin is the benchmark for comparison, let’s look at how all three fast-acting insulins stack-up against it.
Of the three, Apidra (insulin glulisine) is the weakest, possessing a slightly weaker binding affinity for the insulin receptor than RHI. However, its binding affinity for the IGF-1 receptor is a full 4-5X weaker. Humalog (insulin lispro) is closer to RHI, with an insulin receptor binding affinity just under RHI, and an IGF-1 binding affinity about 1.5X higher. Novolog (insulin aspart) is the strongest of the bunch, with an insulin receptor binding affinity similar to Humalog, but an IGF binding affinity 4-5X higher than regular human insulin. This makes Novolog the most potent of the fast-acting insulins, but also the most mitogenic.
The next insulin on the list is NPH (neutral protamine hagedorn), also known as Humulin N/Novolin N. I am not going to spend much time on this intermediate-acting insulin, simply because I see no need to. I think it’s a poor choice for bodybuilders for several reasons. First of all, it’s the least consistent in terms of absorption rates. With an onset time of 1-4 hours and duration of action ranging from 9 to 16 hours it’s just too unpredictable for bodybuilders, who tend to time their insulin use according to their food intake. Furthermore, if one is looking for a sustained elevation of insulin levels, why not just use the longer-acting insulins, such as Lantus or Levemir, both of which provide all the benefits of NPH, but with a much more consistent release rate.
I don’t consider mixed insulin preparations to be any better. Mixed insulin products are those which combine more than one type of insulin in the same vial. Although these can be useful for diabetics, non-diabetic bodybuilders do not require this type of layered release in order to properly manage blood glucose levels. If you are contemplating insulin use, you are better of choosing something else.
Finally, we come to the long-acting insulins—Lantus (insulin glargine) and Levemir (insulin detemir). First off, I want to say that despite being the least likely to cause hypoglycemia I don’t consider them appropriate for beginners, and as with all newer drugs, we are still learning how to best use them. Even in my own coaching practice, my opinions regarding their optimal application have changed dramatically within just the last 6 months. More than any other form of insulin, these are the most likely to cause insulin resistance, especially at higher dosages. This makes frequent, long-term use a bad idea. Furthermore, if used inappropriately, fat gain is likely.
Between the two, Lantus has a longer duration of action (about 24 hours) and a more even release rate, with little to no discernible peak. On the other hand, Levemir stays active for 12-24 hours, depending on dose, but that isn’t the only difference between the two. When it comes to IGF-1 binding, these two drugs are at the opposite ends of the spectrum. In short, Lantus is an IGF-1 powerhouse. With a binding affinity 6-8X that of RHI (some studies have shown it to be up to 500X higher, although this is certainly incorrect), it exceeds all other insulins in this regard.
When it comes to its effect on IGF-1 levels, research has shown it to be the only insulin capable of elevating IGF-1 levels beyond what is seen with regular human insulin. The most likely mechanism for this is the absence of IGF-1-like activity at the pituitary. This, combined with its impressive binding affinity, should technically make Lantus the most anabolic form of insulin available. This doesn’t necessarily mean it’s the best (what is “best” can change from person to person), but in my experience, it can be helpful for breaking past plateaus. So long as it is used properly, insulin sensitivity can be maintained.
If Lantus is the most anabolic insulin, then Levemir is the least. With an insulin and IGF-1 receptor binding affinity weaker than that of regular human insulin, it is low man on the totem pole. Of course, it will still perform all the physiological functions normally associated with insulin, but with a comparatively reduced, overall anabolic effect. From a bodybuilding standpoint, there are no known advantages to using Levemir over Lantus, but from a harm reduction standpoint, it is yet to be determined.
One concern among researchers is Lantus’s exaggerated mitogenic potency, which is directly connected to its greater IGF-1 binding/production. As mentioned earlier, the greater insulin’s mitogenic potency, the more likely it is to induce cell division in mitotic cells, such as cancer cells. While this will not cause cancer, it could be a big problem for someone who already has cancer, causing it to grow at an accelerated rate and/or metastasize. Several studies have been conducted with conflicting results (recent studies have shown no negative effects in this area).
Although this might sound scary, when one looks at the bigger picture, it becomes apparent that it is really only a minor concern. Not only do bodybuilders use Lantus much less frequently than diabetics (if they’re smart), but a drug like growth hormone, which directly increases IGF-1 levels to a far greater degree than insulin (especially at bodybuilder doses), is a significantly greater risk factor. Yet, bodybuilders routinely engage in its use without even the slightest concern for its effect on cell division. Therefore, it seems kind of silly to place our attention on Lantus when other PED’s are much more likely to have a negative effect in this area.
With so many different types of insulin available on today’s market, trying to determine which one is best can be a difficult task for many bodybuilders. When used properly, the benefits on recovery and growth are substantial and side effects minimal. On the other hand, improper use is likely to lead to metabolic dysfunction and eventually, damage to one’s physique. Hopefully, the information presented herein will help eliminate some of the initial confusion and point you in the right direction.
