Serotonin Levels Shown to Impact Bone Mass

Serotonin is a neurotransmitter manufactured in the brain that has a major impact on mood, learning, appetite and sleep… right? Yes, insofar as it goes… but once again digestion expert Andrew L. Rubman, ND, wants us to know there is more to the story. It turns out that 5% or less of the body’s serotonin is made in the brain, while 95% is manufactured in the gut. Not only that, new research has also found that this gut-derived serotonin, which is different than that manufactured in the brain, plays a major role in bone formation. Yet again we learn, everything in the body relates to everything else.

I sat down with Dr. Rubman to learn more about what these findings mean to our health — physical as well as emotional — since most people equate serotonin with mood and not much else. He made no bones about his hopes that the finding will be used to help improve overall health, not just as the rationale for development of a new anti-osteoporosis drug.


Interestingly, this particular research finding was an incidental one. Researchers at Columbia University College of Physicians and Surgeons happened upon the link between serotonin and bone density while studying the role of the Lrp5 gene in one form of osteoporosis. Working primarily with mice, they set out by introducing genetic mutations that reduced production of the Lrp5 gene in the gut. This caused higher than normal levels of gut serotonin and also low bone mass. Next they introduced a mutation that increased Lrp5 activity, which resulted in lower levels of gut serotonin and denser bones. The investigators were surprised to find that Lrp5 regulates the production of serotonin in the gut. Further research is needed to confirm and expand upon these results, which were published in the November 28, 2008, issue of Cell.

Dr. Rubman applauds this research, being hailed as a landmark study, for confirming what had previously only been suspected, but notes that many blanks need to be filled in. For instance, will altering the levels of gut-produced serotonin turn out to affect mood, even indirectly? What happens to digestion if you manipulate the process of serotonin production in the gut? Are there other factors not yet identified that will be affected by taking such action? Is there a natural cycle we don’t yet understand?


In reality, the extent to which life’s bumps are smoothed out is affected by how much serotonin is manufactured in the gut as well as the brain, says Dr. Rubman, noting that inevitably the function of the digestive tract impacts the central nervous system and therefore, the brain. “We always need to look at the community of influence,” he said, pointing out that a well-known example of this is irritable bowel syndrome, which is linked with emotional aspects as well as digestive ones. Tinkering with the production of serotonin in the gut may indeed someday lead to new solutions to one problem — preventing osteoporosis — but before that is set in motion, we must understand more about what else will happen too.

One thing that is known is that gut-produced serotonin does not cross the blood-brain barrier (as SSRI class drugs do), and so is not directly related to that manufactured by the brain. But Dr. Rubman reminds us that this does not mean it doesn’t play a role in stress. For example, think about that queasy feeling you get in your stomach before making a speech or opening your credit card bill. Both kinds of serotonin — that produced in the gut as well as that produced in the brain — help soothe this type of stress by contributing to our ability to maintain equanimity in the face of challenges.


The best strategy to promote health and suppress disease processes is to enhance normal function, observes Dr. Rubman, adding that this research is a good illustration of why, whenever and wherever possible, this should be accomplished without the assistance of medication. It’s like that old children’s song about how all the bones connect to one another — but in this case, the bone turns out to be connected to everything else in the body, too.