Osteo and Gut Serotonin

As published in the online Cell Journal
www.cell.com/abstract/50092-8674(08)01255-5,
It is interesting but will have to see what others make of it. And if true, then what comes next. However we still can't relate bone mass to fracturability. So we will have the "cart before the horse".

SUMMARY

Loss- and gain-of-function mutations in the broadly expressed gene Lrp5 affect bone formation, causing osteoporosis and high bone mass, respectively. Although Lrp5 is viewed as a Wnt coreceptor, osteoblast-specific disruption of -Catenin does not affect bone formation. Instead, we show here that Lrp5 inhibits expression of Tph1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum. Accordingly, decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice, and gut- but not osteoblast-specific Lrp5 inactivation decreases bone formation in a -Catenin-independent manner. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents ovariectomy-induced bone loss. Serotonin acts on osteoblasts through the Htr1b receptor and CREB to inhibit their proliferation. By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study broadens our understanding of bone remodeling and suggests potential therapies to increase bone mass.

By SharonG
Posted November 30, 2008 at 11:27 am
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Heard about this on National Public Radio the other day. First thing that came to my mind was the possible affect of depression on serotonin levels.
Sharon

By Eamenard
Posted November 30, 2008 at 4:01 pm
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The New York Times article by Gina Kolata stated that the gut serotonin is different than the brain serotonin and 95% of the body's serotonin is produced in the gut. Furthermore the gut serotonin can't get thru blood brain barrier.

Evidently the Rx for depression must be able to get thru as we take it by mouth.

From the Times article- "Karsenty reports, though, that gut serotonin can directly control bone formation. It is released into the blood, and the more serotonin that reaches the bone, the more bone is lost."

The Times article has a broader overview than the Cell and goes on to say that it is genetic. I would recommend reading it.

By zeta
Posted November 30, 2008 at 5:37 pm
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Just thought for those interested I would give the NYT article link, which as Eamenard mentions has a broader overview:

http://www.nytimes.com/2008/11/27/health/research/27bone.html?partner=rss&e mc=rss

zeta

By huessysignoret
Posted November 30, 2008 at 7:23 pm
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Zeta -- the work on serotonin is astonishing. Here's a question: I have difficulty sleeping. Anti-depressants help me sleep through the night, but have other side effects, unpleasant, which have caused me to reject them. My psychiatrist suggested taking L-tryptophan, the precursor to serotonin, to aid with sleep. It does help. But here's the question: I was already osteoporotic, so taking the amino acid has not led to osteoporosis, but is it possible that taking l-tryptophan could actually worsen the osteoporosis? Does anyone know if the research supports that proposition?

(Yikes -- are there dragons behind every door?)

By PikaB
Posted December 1, 2008 at 9:35 am
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"First thing that came to my mind was the possible affect of depression on serotonin levels."

There have already been a number of studies linking depression to osteoporosis. There are also several studies linking SSRI anti-depressants to osteoporosis, but it is unclear whether those anti-depressants are really linked (perhaps the only link is the underlying depression). Still it seems prudent that people with a combination of osteoporosis and depression should try to avoid SSRI anti-depressants if possible.

By zeta
Posted December 1, 2008 at 1:51 pm
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Hi huessysignoret,

I think this new research on serotonin and its potential link to osteoporosis is very exciting, but I think it is way too early to say that higher serotonin levels will worsen osteo. So, if tryptophan helps you and keeps you off SSRI anti-depressants, I would keep taking it, though of course I can't make that decision for you. Some folks also take the precurser to tryptophan, a supplement I can't remember the name of right now (5HTP) or something?? for migrains.

So no I don't think this research supports the notion that increasing your serotonin level, in your case via tryptophan, means it will make your osteo worse. I can relate to what you say though about the dragons, but we have to live in the moment, day-to-day, and sleep deprivation is bad for us in so many ways, including bad for osteo.

zeta

By huessysignoret
Posted December 1, 2008 at 2:03 pm
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Thanks -- and needless to say, the advice I was hoping I might hear. Being on an SSRI anti-depressant was causing severe myoclonus (hand tremors, whole-body twtiches.) I could barely button my blouses or put on my watch, and never knew if my spoonful of cereal would end up in my mouth or fly over my left shoulder!

Some years ago, I believe L-tryptophan was actually banned, because it caused some very bad side effects -- maybe even death? But it turned out that the problem came from the dye used to encapsulate the amino acid, not from the tryptophan itself. And yes, it is helpful for sleep, and the more prescriptions I can stay off, the better!

Thanks again,

Pam

By Pragmatic
Posted December 5, 2008 at 3:05 am
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Hi there,

Caveat: I formulated TotalSleep (link to science part: http://www.fluidessentials.com/ourscience.php?section=totalSleep)

I'd stick with L-Trytophan as it increases brain serotonin. 5-HTP is absorbed in the gut (hence reports of gastric distress). A portion of 5-HTP passes through the gut and crosses the blood brain barrier. In any case, I'd stick with L-Tryptophan.

Stress, anxiety, depression, age, normal hormone cycles and inflammation all deplete Tryptophan. Big correlations between inflammatory diseases and sleeplessness and depression because Tryptophan is depleted. Tryptophan begins the natural sleep cycle.

Regarding osteroporosis, Vitamin D and Vitamin K are great.

If anyone wants details on osteoporosis, you can Google peroxynitrites, superoxide anion, nitric oxide and osteoporosis.

Take care! Great posts!

By huessysignoret
Posted December 5, 2008 at 8:44 am
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Another member posted something saying Vitamin K was useless for osteoporosis. Can you tell me more about Vitamin K? Can you get it from food, or do you need a supplement? What does it do?

Thanks,

Pam

By dearme
Posted December 5, 2008 at 11:37 am
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A fascinating discussion! Where do you find the time to do all the research?! Quite astonishing. My butt rarely hits a chair during a normal day and when it does I wouldn't choose medical research to juice my imagination. Y'all are amazing people!
Another thing - there's no depression in my family that I know of and yet every 3rd female has or has had osteoporosis. Such a mysterious malady.

By Jacqueline
Posted December 6, 2008 at 5:22 pm
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Huessysignoret - You might want to consider trying melatonin to help you sleep better. I wonder what members of this community think about this, especially in light of the new research about gut sertonin. I've been taking melatonin lately, and I am sleeping better.

By Raven1
Posted December 6, 2008 at 5:44 pm
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This is a really interesting article. A problem with Forteo is the delivery system and expense. Perhaps the gut serotonin will alter everything and we can look forward to a new bone growth medication that doesn't have to be injected, but can be swallowed and processed in the gut. I only have 11 months left on Forteo and I don't like the bisphosphonates. Interesting!

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