Osteocalcin: A bone hormone that promotes a healthy gut

A healthy gut obviously depends quite a bit on diet. The quickest way to an unhealthy gut is a high calorie, low quality diet. But diet is only one factor in shaping gut health.

In the last blog I covered the gut hormone GLP-1. If you didn’t read that blog, check it out here because it will help. GLP-1 is a hormone secreted by different parts of the gut via different stimuli. It primarily senses the presence of nutrients and modulates gut motility.

GLP-1 also plays a role in regulating insulin secretion and blood glucose levels. I’ve mentioned numerous times how important insulin and proper blood glucose regulation are to a healthy gut.

As it turns out, GLP-1 has a little help from another hormone. Bone secretes a hormone called osteocalcin that plays a role in nearly every function that GLP-1 performs. As a result, paying attention to both is important for both gut and overall health.

Osteocalcin and a healthy gut

Bone forming cells called osteoblasts secrete osteocalcin, a hormone with wide-ranging effects in multiple tissues that follows a circadian rhythm. In fact, the circadian rhythm of cortisol drives the osteocalcin rhythm.

Osteocalcin exists in 2 forms: carboxylated and uncarboxylated. The carboxylated version holds calcium in bones and releases it when we need it. Uncarboxylated osteocalcin circulates in the blood where it acts on different tissues.

When osteocalcin makes it to the gut, it promotes the release of GLP-1. Thus, osteocalcin is a bone derived hormone that modulates gut motility. In the stomach and upper small intestine, it decreases motility to help fully digest your meal. In the lower small intestine and colon, it increases motility and promotes proper stool consistency.

But the effects of osteocalcin on insulin secretion and glucose may be just as important for gut health.

Osteocalcin for a healthy gut

Osteocalcin, GLP-1 and insulin secretion

In a healthy person, insulin sensitivity and blood glucose follow a pretty strong circadian rhythm. We attribute part of this to the fact that you’ve normally fasted for 12 or more hours in the morning. But if it were simply due to fasting, Type 2 diabetes would be an easy fix.

Instead, a number of hormones help drive the circadian rhythm of insulin sensitivity. GLP-1 follows a circadian rhythm, driven both by regular feeding time and by light exposure. GLP-1 secretion is greatest when food is consumed right before the active period and declines through the day. Additionally, GLP-1 causes greater insulin secretion at this time.

Osteocalcin follows an identical rhythm and leads to an identical response to insulin. In other words, osteocalcin peaks right before the active period when it causes the greatest insulin response to food. In addition to increasing GLP-1, uncarboxylated osteocalcin binds to the pancreas and causes insulin secretion directly.

As mentioned above, insulin plays a role in regulating gut health. Hyperglycemia causes leaky gut, but insulin blocks this effect. Additionally, insulin decreases blood glucose and makes hyperglycemia less likely. So in addition to promoting gut health along with GLP-1, a strong osteocalcin rhythm directly protects against leaky gut.

Both osteocalcin and GLP-1 improve insulin secretion by:

  • Increasing the number of insulin secreting beta cells in the pancreas
  • Bolstering insulin synthesis
  • Increasing insulin storage

In addition to effects on the pancreas, both GLP-1 and osteocalcin increase insulin sensitivity in muscle and fat. Type 2 diabetics have lower levels of both GLP-1 and uncarboxylated osteocalcin.


An healthy gut requires a lot more than a focus on diet. Many other factors help set the stage for healthy digestion. Osteocalcin, a hormone secreted from bone, plays a role in regulating gut motility as well insulin secretion.

Insulin is a hormone that plays a large role in gut health. It helps set circadian rhythms to the feeding cycle and protects against leaky gut. It’s also an important hormone for regulating metabolism throughout the body.

Given that osteocalcin is secreted by bone-forming osteoblasts, maintaining bone and muscle mass are crucial to a healthy osteocalcin circadian rhythm. Avoiding or reversing Type 2 diabetes is also important, as insulin resistance inhibits osteoblast function.

Want to learn how to get the most out of osteocalcin? Things like what nutrients you need and what you should do? We developed a 3-part series on vitamin K for our email subscribers that you can grab right now, by signing up for our email list.

If you haven’t guessed, vitamin K is particularly important!

To find out what else matters, just enter your name and email in the form below and you’ll receive our version of “Everything you wanted to know about vitamin K and osteocalcin but were afraid to ask” over the course of the next week.

5 thoughts on “Osteocalcin: A bone hormone that promotes a healthy gut

    • cincodm says:

      It’s part of diet and exercise. It’s not something I’d take, it’s something that tells us what’s important about our behavior to promote overall health.

    • cincodm says:

      It and K1 act as a coenzyme in the carboxylation of osteocalcin to help hold it in the bone. It does nothing in regard to the synthesis. It basically helps bind calcium to hold in the matrix.

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