More than decade ago I was reading one of the article’s on Ray’s website, in which he described the potent catabolic effects 5-HT has on bones. In other articles and interviews, Ray also discussed the catabolic effect of 5-HT on muscles. However, whenever people asked him about bone health, especially in the context of aging, Ray seemed to almost always bring up 5-HT and the fact that anti-serotonin drugs are anabolic for bones. While 5-HT may have direct catabolic effects of its own, it seems plausible that the main mechanism of action for the catabolic effects of 5-HT on bones (and muscles) stem from the ability of 5-HT to activate the HPA axis and thus raise cortisol levels. Cortisol’s role as a catabolic hormone for both bones and muscles is undisputed even by mainstream medicine. 5-HT activates the HPA axis through the 5-HT2C receptor and antagonists of that receptor have not only been shown to stop/reverse conditions of glucocorticoid excess (Cushing disease/syndrome), but also reverse osteopenia/osteoporosis in animal models, as well as ameliorate/stop cachexia (soft-tissue wasting). To my knowledge, the study below is perhaps the first to formally recognize the role of 5-HT (as well as its precursor and breakdown products) in human osteoporosis, both as a biomarker and a potential cause of the condition. The study findings are very impactful due to their potential of providing a simple, safely-tested biomarker for osteoporosis (e.g. whole blood 5-HT), Namely, the prophylactic, diagnostic and follow-up “standard of care” for osteoporosis currently is the so-called DEXA scan, which exposes the patient to large amounts of ionizing radiation – a known human carcinogen. If 5-HT is confirmed as a reliable biomarker of osteoporosis then it could potentially entirely replace the DEXA scan and thus prevent a large number of secondary cancers diagnosed each year as a result of iatrogenic ionizing radiation exposure. The findings of the study also suggest a simple therapeutic option in the form of 5-HT antagonists. Some of the widely used 5-HT antagonists such as cyproheptadine, diphenhydramine, ondansetron, etc have bee on the marker for decades and have a very well-known and low-risk pharmacological profile. Such drugs are certainly preferable to the current ostoporosis treatments, especially the carcinogenic estrogen HRT or the highly inflammatory synthetic PTH peptide injections.
https://doi.org/10.17305/bb.2025.11513
“…The study found that key serotonin pathway markers—specifically 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA)—were significantly higher in women with osteoporosis compared to those with normal bone density or osteopenia (a precursor to osteoporosis). These markers rose progressively as bone mineral density decreased. The research revealed that measuring these serotonin-related compounds could improve diagnostic accuracy for osteoporosis. A combined blood panel of 5-HTP, 5-HT, and 5-HIAA showed a diagnostic accuracy of nearly 90%, outperforming traditional bone density measurements in some cases. Higher levels of these serotonin markers were also linked to a longer time since menopause, suggesting that the serotonin pathway plays a role in the progression of bone loss over time. The findings point to the potential for using these biomarkers not only in diagnosis but also as part of strategies to delay the onset of osteoporosis, especially in women experiencing prolonged menopause.”
