Hyperplasia: A summary

We're probably all familiar with hypertrophy, or the biggening of muscles. It gets talked about a lot, and comes in two forms:

  1. Sarcoplasmic hypertrophy, or increased muscle glycogen storage;
  2. Myofibrillar hypertrophy, which focuses more on increased size of myofibril (individual muscle cells).

Hyperplasia gets talked about a lot less. So what is it?

Visually Showing Hypertrophy and Hyperplasia

The difference between hypertrophy and hyperplasia is best shown through a simple diagram. Both are examples of cellular adaptation.

What is Hyperplasia, Exactly?

It can be described as an increase in the amount of organic tissue due to cell proliferation. In the context which we are talking, this would be an increase in muscle size due to an increase in the number of muscle cells. This can happen in a variety of ways, but I'm going to summarize the Pathological & Physiological reasons which are the two that relate to PEDs use and exercise.

Pathological Responses

Growth hormone (and by extension IGF-1) are correlated with increases in the number of cells in primates

To investigate the effects of GH/IGF-I augmentation on mammary tissue in a model relevant to aging humans, we treated aged female rhesus monkeys with GH, IGF-I, GH + IGF-I or saline diluent for 7 weeks. IGF-I treatment was associated with a twofold increase, GH with a three- to fourfold increase, and GH + IGF-I with a four'-to fivefold increase in mammary glandular size and epithelial proliferation index. These mitogenic effects were directly correlated with circulating GH and IGF-I levels, suggesting that either GH or its downstream effector IGF-I stimulates primate mammary epithelial proliferation.

This data is replicated many times and in many different animals. For example, GH treatment increases IGF-1 mRNA in rats by 20x.

In humans, this translates... kinda. There are similar roles for GH & IGF-1 between animals and humans in terms of hyperplasia. Folks with a GH deficiency have more fat and less muscle. It stands to reason that increasing GH (and/or IGF1) will induce hyperplasia.

There's a catch, tho. /u/MezDez has an excellent write up on how supraphysiological levels of GH. Key to this article is this quote:

Observations in people with acromegaly suggest that chronic high levels of circulating GH and IGF-I may actually be detrimental to muscle function.

So better body composition, larger muscles, but at the cost of muscle function and at the risk of looking kinda weird.

Exercise / Physiological response

While we often consider exercise as only inducing muscle hypertrophy, direct counts of muscle fibers in lab animals shows that exercise will also increase the number of muscle fibers. For animals that were engaged in forced overload stretch or exercise increased the number of muscle fibers by 9-52% (direct count) or 10-82% (inferred using cross-section) in multiple models.

Data in humans is lacking cos ain't nobody gonna be approving or volunteering for a study that cuts open your leg to count muscle fibers.

The best way to induce hyperplasia in humans through exercise is a relative unknown. There's a bunch of bro-science on it, recommended routines, but it's all educated guess work at this point, based on what we've subjected lab animals to. (There's a pretty good opinion piece from a Dr Jose Antonio about it available here))

My only specultation here based on my own review would be frequency of training is likely to induce hyperplasia, but we really don't know.


Study 1, HGH - 96 athletes with an average age of 28 were given 2mg/d subq (which is considered a low dose). Performance improved acrossed the board, an average of 1.4kg of body fat was lost, while 2.7kg of lbm was gained (Wow!).

Study 2, MK677 - 60-80 year olds, with low starting levels of GH. MK677 significantly increased 24h mean GH against placebo. Starting point for this group was 0.6ug/L which is sigificantly below normal (1.3ug/L). Supplementation also brought them up to or near the normal GH level. It also increased IGF by about 30%.

Study 3, MK677 - 50+ year olds with Alzehimers. MK677 significnatly increased IGF1 by 60% within 6 weeks.

In all these three studies, it's impossible to say hyperplasia occurred, but it seems highly likely in study 1 (HGH). MK677 definitely had an impact, but given its agonist nature (i.e. it's not a replacement for your natural GH like HGH is) the increases are not going to cause large changes in mean levels - only increase the size of the natural spikes.

Personal Opinion - HGH, MK677 or other secretagogues

These compounds increase GH, and may result in hyperplasia depending on dose and length of application. HGH certainly would, and MK677 seems to. The changes in GH (and by proxy IGF) do make possible hyperplasia based on our understanding for the conditions in which hyperplasia needs to occur under, which is why I introduced these studies. We're limited in the conclusions we can make for MK677 due to the target audience and lack of studies on healthy young adults.