![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 25. This is the beginning of the thread.
Posted by Larry Hoover on December 6, 2008, at 9:05:43
There was a paper published late last month that really got me thinking. For the first time, it's been shown that processes occurring in the gut can have a profound effect on bone formation by regulating the number, and thus the activity of, osteoblasts. Bone is constantly being formed and destroyed by cells called osteoblasts and osteoclasts, respectively. Assuming that the body has the mineral resources to allow them to function properly, it's the balance between the activity of the two that determines bone density.
I'll post the abstract to the paper, and an article about the paper at the bottom. I'll try and give the gist of it, and discuss why I think it's an important finding.
The amino acid tryptophan, from dietary protein, is absorbed in the duodenum. Cells lining the duodenum express the enzyme tryptophan hydroxylase (TRP), which converts tryptophan into 5-hydroxy-tryptophan (5-HTP, also available as a supplement). It turns out that it's the activity of this enzyme in the duodenum that largely determines blood serotonin concentration, as 5-HTP is rapidly converted to serotonin by an enzyme that is common-place throughout the body. It had been thought that it's the liver that regulated this, but it turns out it's the gut.
Serotonin circulating in the blood regulates the proliferation of osteoblasts. Low levels of serotonin lead to high proliferation rates of osteoblasts, and in turn, high bone formation rates. In contrast, high serotonin levels suppress osteoblast proliferation. This may explain the finding that some antidepressants are associated with loss of bone density, because they can shift a vulnerable person's bone synthesis balance into the negative range.
In the referenced paper, the researchers tweaked the process at various points (in mice), and found they could control bone density quite predictably. What this suggests is that entirely new therapies for osteoporosis are possible. Rather than merely slowing bone loss, it might easily be reverted.
The biochemical regulatory sequence allows intervention at four points, as I see it.
First, gut tryprophan hydroxylase activity is regulated by an LDL (low-density lipoprotein) receptor. High activity at that receptor suppresses TRP. I'm not sure that messing around at that level would be clear-cut, as we're still very much in the dark with respect to cholesterol regulation.
Second, the peripheral tryptophan hydroxylase enzyme (TRP type 1) could be inhibited. That was tried in the mice, and it worked. Bone density increased, even in mice genetically predisposed to low bone density. Because there is a completely separate enzyme behind the blood brain barrier, a peripheral inhibitor would not affect brain serotonin synthesis.
Third, you could inhibit the peripheral aromatic decarboxylase enzyme. Carbidopa is one such drug, and it is given with the dopamine precursor L-DOPA in treatments for Parkinson's disease, to prevent dopamine forming outside the brain. The very same enzyme converts 5-HTP to serotonin, so we already have one intervention available. I've never heard of carbidopa being used to treat osteoporosis, but hey! Who knows. As an aside, I earlier mentioned that the gut creates 5-HTP from tryptophan, and that's what leads to high blood serotonin and bone loss. That would mean that 5-HTP supplements would predispose to osteoporosis, also. I'm thinking that 5-HTP would best be taken with carbidopa, if that's someone's antidepressant strategy.
Fourth, and perhaps most promising, as it acts directly at the point of regulation of osteoblast proliferation, is that they could block the specific serotonin receptor involved (called Htr1b). They were able to do that in the mice, and osteoblast activity was up-regulated, leading to higher bone density.
So, promising new leads, methinks. I'd expect human trials before too long, as none of it is too far beyond our current capabilities.
Here are the abstract, and the article discussing the research. N.b., the article has an error in the second last paragraph. I believe it should say "lower" rather than "higher".
Regards,
Larhttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=1904174
Cell. 2008 Nov 28;135(5):825-37.
Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.
Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G.
Department of Genetics and Development, Columbia University, New York, NY 10032, USA.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 beta-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 beta-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.
http://www.medpagetoday.com/Endocrinology/Osteoporosis/11923
Serotonin in Gut Linked to Bone Formation
NEW YORK, Nov. 26 -- That Thanksgiving turkey may be bad for your bones. That's one of the implications of a study that -- for the first time -- links the gut to bone formation, according to Gerard Karsenty, M.D., Ph.D., of the Columbia University College of Physicians and Surgeons, and colleagues. The research, conducted mainly in mice, links serotonin produced in the duodenum to the proliferation of osteoblasts, the cells that create new bone, Dr. Karsenty and colleagues reported in the Nov. 26 issue of Cell. "This is totally new," Dr. Karsenty said. "We had no clue that the gut had control over bone, and in such a powerful manner."
The findings open up the possibility of controlling such diseases as osteoporosis either by a diet low in tryptophan -- the raw material for serotonin synthesis -- or by inhibiting the serotonin-osteoblast interaction with medications.If diet turns out to be a possible approach, the turkey may have to go --it's one of the best dietary sources of tryptophan.
Until these experiments, Dr. Karsenty said, the function of gut-associated serotonin was not known.
"The findings demonstrate without a doubt that serotonin from the gut is acting as a hormone to regulate bone mass," he said.
But the discovery was accidental. The researchers were investigating the role of a protein known as LDL-receptor related protein 5 (or LRP5), which causes osteoporosis pseudoglioma when mutations lead to a loss of function.
Other mutations in LPR5, which presumably cause overactivity (gain-of-function mutations), are associated with diseases characterized by high bone mass, the researchers noted.
The first hint of a link to serotonin came when they noted that a key player in the molecule's synthesis -- the enzyme tryptophan hydroxylase 1 (or Tph1) -- is highly overexpressed in the duodenum of mice lacking LPR5.
Tph1 is the enzyme that limits the rate at which serotonin is produced in the gut. Indeed, 95% of the body's serotonin is produced in the gut; because it does not cross the blood-brain barrier, a second enzyme, Tph2, is responsible for serotonin in the brain.
In mice lacking LRP5, levels of Tph1 are normal at birth and begin to show significant increases (at P<0.01) compared to wild-type animals at two weeks of age.
The low bone mass syndrome in those animals begins to appear two weeks later.
In parallel, serum serotonin levels also increase as the animals age, the researchers noted.
Interestingly, the researchers noted, in an earlier case-control analysis of three patients with osteoporosis pseudoglioma, serum serotonin levels were four- to five-fold higher than in six age-matched controls.
In an in vitro experiment, the researchers found that serotonin inhibits osteoblast proliferation, so they fed mice a diet with 75% less tryptophan than normal.
In mice lacking LPR5 -- and therefore prone to low bone mass -- the diet decreased circulating serotonin levels eight- to 10-fold (without affecting serotonin in the brain) and normalized both bone mass and bone formation parameters.
A similar experiment, using a compound that blocks serotonin synthesis, had nearly identical results.
The researchers also found that only one of the three serotonin receptors on osteoblasts (a molecule dubbed Htr1b) is involved in the process -- blocking the other two had no effect on bone mass, while blocking Htr1b increased the number of osteoblasts, bone mass, and the bone formation rate.
In a final experiment, they engineered mice lacking the gene for Tph1 and removed the ovaries from female animals at six weeks of age. At three months, bone resorption had increased, but the animals had not developed low bone mass because they were still building new bone.
That experiment in particular holds out clinical promise, Dr. Karsenty said. "Osteoporosis is often diagnosed when the damage to bone is already significant and fracture risk is already too high," he said. "We need something to build bone, not just prevent or repair its loss."
The cells that produce serotonin come in contact with drugs that pass through the gastrointestinal tract, he said, so reducing gut-associated serotonin should be relatively simple to achieve with a drug.
Dr. Karsenty said he thinks there should be few side effects of such a drug, since patients with high bone mass often have circulating serotonin levels as much as 50% higher than normal without other symptoms.
He added that he sees no theoretical obstacles to finding medications that modulate the body's serotonin. "If we can do it in the brain," he said, "we can do it in the body."
Posted by Quintal on December 6, 2008, at 10:20:47
In reply to serotonin and bone density, posted by Larry Hoover on December 6, 2008, at 9:05:43
Thanks for posting the paper, and pointing out the error at the end. Obviously, as a tianeptine user I'm wondering what effect it might have on bone density. I take lansoprazole most days and it has been associated with an increased risk of hip fracture.
Q
Posted by Phillipa on December 6, 2008, at 10:55:34
In reply to Re: serotonin and bone density » Larry Hoover, posted by Quintal on December 6, 2008, at 10:20:47
Do have osteoporosis. But low levels of SSRI's increasing now but that doesn't mean that it would affects to bones does it. Endo attributes to synthroid and hasimotos thyroiditis and suggests vita D with Cal and mg. Can't afford the pricey boniva and actonel and too many abd side effects. Know serotonin levels are different in brain. So how does taking an SSRI differe from eating turkey which produces tryptophan? So you're thinking a med that stops the gut absorption of serotonin would help with osteoporosis? Phillipa
Posted by Larry Hoover on December 6, 2008, at 12:47:43
In reply to Re: serotonin and bone density » Larry Hoover, posted by Quintal on December 6, 2008, at 10:20:47
> Thanks for posting the paper, and pointing out the error at the end. Obviously, as a tianeptine user I'm wondering what effect it might have on bone density. I take lansoprazole most days and it has been associated with an increased risk of hip fracture.
>
> QYou're welcome.
Tianeptine may be the only drug yet identified that directly reduces blood serotonin levels. Well, that's what this ten year old study declares: http://www.ncbi.nlm.nih.gov/pubmed/9807972
A reduction in circulating serotonin would enhance bone formation, so you should be comforted that your antidepressant choice has the potential of producing a corollary benefit. We hear so much of side effects, which are characteristically negative. This would be a side effect, but as it is positive, I'd prefer to call it a side benefit. ;-)
As to the proton-pump inhibitor, the mechanism by which this occurs has not been identified. It might be little more than reducing solubility of dietary calcium with the change in stomach acidity. One Danish study showed that the effect was not significant until about 7 years of continual use. That might also implicate B12 deficiency, therefore, as it can take years to deplete liver stores of this nutrient; B12 also requires an acid stomach environment to promote absorption. So, bump up the calcium and vitamin D intake, and take a B12 supp, preferably a sublingual.
An alternative might be the H2-atagonist drugs, e.g. cimetidine, famotidine, ranitidine, or nizatidine. They are associated with a decreased risk of fracture. I have no idea why that might be the case.
Regards,
Lar
Posted by Larry Hoover on December 6, 2008, at 12:54:16
In reply to Re: serotonin and bone density, posted by Phillipa on December 6, 2008, at 10:55:34
Anything that increases blood serotonin would suppress bone formation, so eating protein high in tryptophan would have a similar effect to taking an SSRI. The thing that can't be predicted is how vulnerable an individual is to blood serotonin influence. There are so many other variables to consider, especially diet (calcium, magnesium, vitamin D intake). Also, post-menopausal women are especially vulnerable already because estrogen suppresses osteoclast (bone-destroying) cells.
The best treatment, IMHO, would be to block the receptor on bone that makes serotonin have an inhibitory effect on bone formation. Then everything else could just go on as before the intervention.
Lar
Posted by bleauberry on December 6, 2008, at 17:54:03
In reply to serotonin and bone density, posted by Larry Hoover on December 6, 2008, at 9:05:43
Very interesting stuff! Thanks for sharing, Larry.
A strange thing happened earlier this year when I was trying St Johns Wort for 6 weeks, and then later when on Lexapro for just a week. I do a ton of walking on my job...a supercenter retail store several times the size of a football field. I got this terrible knife like pain in the heals, right on the ball where I walk. I know what a broken bone feels like, and it was so similar to that it was scary. It was definitely without any doubt bone pain. You can see where I'm going with this based on the info you presented, so enough said.
Any ssri causes me bone pain in the hips, probably the second most used part of my body at work.
I've seen articles from Europe where they scoff at how stupid we Americans are with 5HTP supplements. They claim most of the 5htp converts to serotonin before it reaches the brain. Only some of it remains for the brain. In Europe it is more common for 5htp to be given with Carbidopa to prevent peripheral conversion and to encourage brain conversion instead.
Posted by bleauberry on December 6, 2008, at 18:21:36
In reply to serotonin and bone density, posted by Larry Hoover on December 6, 2008, at 9:05:43
This topic makes me ponder about the many mysterious ways Tianeptine might work, as it takes serotonin out of plasma circulation and into cells. As the data hints, there is a lot of interplay between all kinds of biologies in the body. Maybe somehow the shift in serotonin reinstructs those tryptophan genes, and likely lots of other genes, leading to something beneficial in the brain?
Posted by Phillipa on December 6, 2008, at 20:37:51
In reply to Re: serotonin and bone density » Phillipa, posted by Larry Hoover on December 6, 2008, at 12:54:16
Lar okay I'm dense so how do you block it? Take the vits and D? Phillipa
Posted by Quintal on December 7, 2008, at 17:35:28
In reply to Re: serotonin and bone density » Quintal, posted by Larry Hoover on December 6, 2008, at 12:47:43
Thanks Lar, I already take extra calcium and vitamin D, but wll look into the B12. I've tried H2 antagonists but they weren't as effective to start with. Sounds like they'd be a better choice for long term use.
Q
Posted by DG77 on December 8, 2008, at 14:01:47
In reply to Re: serotonin and bone density » Larry Hoover, posted by bleauberry on December 6, 2008, at 17:54:03
> I've seen articles from Europe where they scoff at how stupid we Americans are with 5HTP supplements. They claim most of the 5htp converts to serotonin before it reaches the brain. Only some of it remains for the brain. In Europe it is more common for 5htp to be given with Carbidopa to prevent peripheral conversion and to encourage brain conversion instead.
>
>
Interesting. I wonder if that would be true of tryptophan supplements as well?
Posted by bleauberry on December 8, 2008, at 16:16:35
In reply to Re: serotonin and bone density » bleauberry, posted by DG77 on December 8, 2008, at 14:01:47
> >
> Interesting. I wonder if that would be true of tryptophan supplements as well?
>I don't know. It does appear to be quite a debate. Some say carbidopa is bad news, others say it is essential. Both sides have valid arguments and solidly believe what they believe. Existing data can be manipulated to support either view.
Posted by Larry Hoover on December 10, 2008, at 17:52:11
In reply to Re: serotonin and bone density » Larry Hoover, posted by Phillipa on December 6, 2008, at 20:37:51
> Lar okay I'm dense so how do you block it? Take the vits and D? Phillipa
I think that's the best approach.
I haven't looked around very hard, yet, but I just read a study on the effect of Prozac on blood serotonin levels, and they went down with time. Not up, down. So, I wouldn't worry about the SSRI issue. You said you have low bone density....your first resort would be calium, magnesium, and vitamin D. Only if that approach didn't work, would I look to more powerful interventions.
Regards,
Lar
Posted by Larry Hoover on December 10, 2008, at 17:56:39
In reply to Re: serotonin and bone density » bleauberry, posted by DG77 on December 8, 2008, at 14:01:47
> > I've seen articles from Europe where they scoff at how stupid we Americans are with 5HTP supplements. They claim most of the 5htp converts to serotonin before it reaches the brain. Only some of it remains for the brain. In Europe it is more common for 5htp to be given with Carbidopa to prevent peripheral conversion and to encourage brain conversion instead.
> >
> >
> Interesting. I wonder if that would be true of tryptophan supplements as well?Tryptophan supps do not lead to significant increases in blood serotonin concentration, most of the time. Some few people do experience that, but it's uncommon.
Lar
Posted by Larry Hoover on December 10, 2008, at 18:21:04
In reply to Re: serotonin and bone density » Larry Hoover, posted by Quintal on December 7, 2008, at 17:35:28
> Thanks Lar, I already take extra calcium and vitamin D, but wll look into the B12. I've tried H2 antagonists but they weren't as effective to start with. Sounds like they'd be a better choice for long term use.
>
> QAre you treating GERD? I used to have that, really bad. I took part in the clinical trial for Nexium (esomeprazole), a proton-pump inhibitor. I *knew* I was getting the real drug, not a placebo. They asked us to try taking it prn (as needed), rather than daily, but I just couldn't do it. I had to take it every day, or I was suffering horribly.
I had had GERD for about twenty years. I never went anywhere without a bottle of Maalox. I tried every antacid drug. I was barely getting by. The Nexium was the best drug I'd tried, but I felt so dependent on it. And I still had a lot of pain. And the reflux was giving me bad asthma, too.
One day I decided to try and learn everything I could about GERD, after reading an article that suggested that GERD sufferers released stomach acid much later after food ingestion than did normal people. They released a normal amount, but it didn't get mixed with food as it was eaten, like it's supposed to. Instead it tended to lie on top of the food, enhancing gas formation, and causing very high local acid concentrations at the top of the stomach. It didn't take much gas moving up the esophagus to carry this excess acid up with it. So, I wanted to understand how the stomach regulates and times acid secretion.
I ended up on Pubmed right through the night. I didn't realize that, until I saw the sun come up. It turns out that there is a critical step in the signalling process that depends on a methylation reaction, which itself depends on vitamin B12 as the carrier. I had already become concerned about nutrient deficiencies caused by stomach acid suppression (resulting in achlorhydria or hypochlorhydria, if you want to understand the effect), and the specific effect on B12 bioavailability. So, when I saw an acid-timing problem caused by deficient B12, I put 2 and 2 together. Vitamin B12 deficiency can exacerbate vitamin B12 deficiency, via GERD.
I started taking 1 mg B12, as well as betaine (a.k.a. trimethylglycine, a methyl donor) and bromelain (proteolytic enzyme from pineapple, to enhance protein digestion). Within a week, I no longer needed Nexium. I couldn't have gone half a day without it, ever before. After more than 20 years of GERD, I didn't have it any more. A decade later, I still don't have the symptoms.
I may not be a typical case. Who knows? But it worked for me.
Lar
Posted by desolationrower on December 10, 2008, at 18:47:18
In reply to Re: serotonin and bone density » Phillipa, posted by Larry Hoover on December 10, 2008, at 17:52:11
> > Lar okay I'm dense so how do you block it? Take the vits and D? Phillipa
>
> I think that's the best approach.
>
> I haven't looked around very hard, yet, but I just read a study on the effect of Prozac on blood serotonin levels, and they went down with time. Not up, down. So, I wouldn't worry about the SSRI issue. You said you have low bone density....your first resort would be calium, magnesium, and vitamin D. Only if that approach didn't work, would I look to more powerful interventions.
>
> Regards,
> Lar
>
these are important, espcially sufficient vitamin D3 - amount in milk or multivitamin is woefully insufficient. need at least several thousand IUs a day if one isn't a lifeguard or farmer or ditch-digger. Also weight-bearing excercise, vitamin k (mk-7 best) also making sure thyroid is adjusted properly. less sodas. and trace minerals also robably help. lactoferrin also looks interesting (from whey protein)-d/r
Posted by Phillipa on December 10, 2008, at 20:11:58
In reply to Re: serotonin and bone density, posted by desolationrower on December 10, 2008, at 18:47:18
Yup here comes my thyroid again which refuses to be regulated with synthroid. Love Phillipa
Posted by fayeroe on December 10, 2008, at 20:23:05
In reply to serotonin and bone density, posted by Larry Hoover on December 6, 2008, at 9:05:43
Thanks, Larry for posting all of this information for us.
As a post-menopausal "person", I know that bone density is a problem for myself...
1. I'm very slender
2. It runs in my family.
3. Bone density test showed I'm "pre".
4. I've taken almost every AD known to man.
It is almost enough to make me depressed. :-)
I don't know which would come first for me, the bone problems or the depression. Meaning, what would I sacrifice if I had to make that decision.
In the meantime I don't eat meat and I make sure that I'm getting enough of the appropriate minerals and vitamins..I can't do much weight-bearing exercise due to the old ankle fracture.
Have I confused you yet? :-) Pat
Posted by Quintal on December 11, 2008, at 11:42:21
In reply to Re: GERD tangent » Quintal, posted by Larry Hoover on December 10, 2008, at 18:21:04
Thanks Lar, my doctor hasn't said exactly what it is. I started having this problem last year when I was using ibuprofen every day, so she thought it might be a patch of inflammation. I've have always had a tendency towards reflux/regurgitation, maybe due to a weakness in my lower esophageal sphincter? I have some of the other symptoms of GERD like excessive salivation and pain on swallowing. Right now I'm having to take 60mg lansoprazole and the pain hasn't entirely gone away yet. It's hard to eat. My doctor was giving me 15mg p.r.n last month but that didn't give much relief. Antacids seemed to make it worse.
I too am concerned about nutrient deficiencies and other imbalances that might happen as a result of excessive acid suppression. I was wondering if abnormal stomach pH has any effect on the digestion of proteins? We were taling about optimum pH of enzymes in class this week and pepsin happended to come up as an example.
I didn't know anything about the process of acid release/production, thanks for the advice. I'm not sure I've grasped it properly. Does this mean B12 deficiency leads to a delay in acid release so even less B12 is absorbed? Which would then be a viscious circle until you correct the problem by supplementing B12 (I suppose via the sublingiual route)? And PPIs might aggravate the underlying problem (even though they treat the symptoms) since they further impair B12 absorbtion?
Q
Posted by Larry Hoover on December 11, 2008, at 18:38:02
In reply to Re: serotonin and bone density, posted by fayeroe on December 10, 2008, at 20:23:05
> Thanks, Larry for posting all of this information for us.
You're welcome.
> I don't know which would come first for me, the bone problems or the depression. Meaning, what would I sacrifice if I had to make that decision.
There is some association between the use of antidepressants and decreases in bone density, but it's pretty hard to draw a causal link. Depression is itself inversely correlated with bone density. With what I've read with respect to the bone serotonin receptors (there are three identified types, possibility of more), it's quite possible that antidepressants bind to those bone receptors. Binding alone might be meaningless, but we'd have to know more about which antidepressant has affinity for which receptor(s), and whether there was an agonist or antagonist effect. It could be crazy-making, trying to analyze it all.
Best to just stick to....
> I make sure that I'm getting enough of the appropriate minerals and vitamins..
Calcium, magnesium, and vitamin D3, especially. Magnesium deficiency blocks calcium uptake by inhibiting conversion of D3 to the active form, 1-25 vitamin D. And by doing so, magnesium deficiency inhibits magnesium uptake. U.S. data show that more than 50% of all sex/age groups fail to obtain recommended magnesium intake levels, even with supplements included in the data.
Supplementing with mag, cal, and D for a couple of weeks should resensitize the body to permit efficient uptake. However, if deficiency of any of the three is well-established, long-term supplementation is recommended.
> I can't do much weight-bearing exercise due to the old ankle fracture.
Have you considered working out in a swimming pool?
> Have I confused you yet? :-) PatNo. Keep trying. ;-)
Lar
Posted by Larry Hoover on December 11, 2008, at 18:56:16
In reply to Re: GERD tangent » Larry Hoover, posted by Quintal on December 11, 2008, at 11:42:21
> Thanks Lar, my doctor hasn't said exactly what it is. I started having this problem last year when I was using ibuprofen every day, so she thought it might be a patch of inflammation. I've have always had a tendency towards reflux/regurgitation, maybe due to a weakness in my lower esophageal sphincter? I have some of the other symptoms of GERD like excessive salivation and pain on swallowing. Right now I'm having to take 60mg lansoprazole and the pain hasn't entirely gone away yet. It's hard to eat. My doctor was giving me 15mg p.r.n last month but that didn't give much relief. Antacids seemed to make it worse.
Have you been tested for Helicobacter pylori? It's the bacterium that is a leading cause of ulcers. Stressors can trigger many of your symptoms. Alternatively, you seem to be describing classic GERD symptoms. Gas pressure can make a competent esophageal sphincter leak, so an upper GI barium x-ray series is often required to see what's really going on.
> I too am concerned about nutrient deficiencies and other imbalances that might happen as a result of excessive acid suppression. I was wondering if abnormal stomach pH has any effect on the digestion of proteins? We were taling about optimum pH of enzymes in class this week and pepsin happended to come up as an example.Absolutely the case. Pepsin is inactive if you suppress stomach acid. That's one reason I started using bromelain. It's not only a good digestive aid, easily breaking down protein, but it's also a potent anti-inflammatory.
> I didn't know anything about the process of acid release/production, thanks for the advice. I'm not sure I've grasped it properly. Does this mean B12 deficiency leads to a delay in acid release so even less B12 is absorbed?Yes.
> Which would then be a viscious circle until you correct the problem by supplementing B12 (I suppose via the sublingiual route)?
Sublingual is best, but high-dose oral supps (I mentioned the 1 mg size) still leads to intestinal uptake, presumed to be via osmosis. In North America, doctors give B12 shots for pernicious anemia, whereas in Europe, they simply use high-dose oral B12. Both work, but I bet the patients prefer avoiding the needle stick.
> And PPIs might aggravate the underlying problem (even though they treat the symptoms) since they further impair B12 absorbtion?
>
> QIndeed. You understood my intent. I struggle to keep from writing a book each time I post.....there are factors and considerations and feedback controls and blah blah. It's really pretty complicated. Your stomach has to sense the presence of food, the type of food, and how much, before it can appropriately secrete acid, enzyme precursors and other substances. Consider the hormone, gastrin http://en.wikipedia.org/wiki/Gastrin
And look at section 1.5 'Factors influencing...'PPIs do indeed treat the symptoms, but they lead to further complications, including dependency on the treatment itself. Moreover, you face iatrogenic (doctor caused) achlorhydria, which is a problem in itself.
Lar
Posted by Quintal on December 12, 2008, at 19:28:43
In reply to Re: GERD tangent » Quintal, posted by Larry Hoover on December 11, 2008, at 18:56:16
I've never been tested for helicobacter pylori, but my dad tested positive a few years back and had a few courses of treatment. I'm not sure how it's spread, I suppose it's possible I have it.
>Absolutely the case. Pepsin is inactive if you suppress stomach acid. That's one reason I started using bromelain. It's not only a good digestive aid, easily breaking down protein, but it's also a potent anti-inflammatory.
Are supplements better than fruit? I eat fresh pineapple about twice a week. I actually thought it might attack the raw stomach lining. Would marshmallow help? I have some old capsules around the house. I was thinking about using up the bottle, but the label warns against taking it within an hour of taking other medicines. Do you know if this is necessary? It makes dosing difficult as I take most of my meds around meal times, and it says marshmallow should be taken with food.
Q
Posted by Larry Hoover on December 20, 2008, at 13:21:59
In reply to Re: GERD tangent » Larry Hoover, posted by Quintal on December 12, 2008, at 19:28:43
Sorry for the tardy reply. My computer power supply failed. Kind of hard to get parts for my 'puter when my 'puter is broken. It's amazing how much I depend on it, without realizing it.
> I've never been tested for helicobacter pylori, but my dad tested positive a few years back and had a few courses of treatment. I'm not sure how it's spread, I suppose it's possible I have it.
Just a thought. The treatment is antibiotics, rather than acid modulation. Infective spread within intimate family relations probably better accounts for familial gastritis trends than what was once thought to be genetic vulnerability.
> >Absolutely the case. Pepsin is inactive if you suppress stomach acid. That's one reason I started using bromelain. It's not only a good digestive aid, easily breaking down protein, but it's also a potent anti-inflammatory.
>
> Are supplements better than fruit?Yes. There is very little bromelain in pineapple, relative to the stems. The commercial product comes from crushing the plant after the fruit is harvested.
> I eat fresh pineapple about twice a week. I actually thought it might attack the raw stomach lining.
I never found it to be an irritant. But just to be sure, I checked the literature and found that bromelain was fairly to markedly effective in treating ulcers about 50% of the time. One lone report simply made a generic statement to avoid bromelain if an ulcer was present, due to a theoretical risk of increased bleeding.
> Would marshmallow help? I have some old capsules around the house. I was thinking about using up the bottle, but the label warns against taking it within an hour of taking other medicines. Do you know if this is necessary?
I had to look it up. Maybe it's a British traditional treatment for dyspepsia? I expect that the mucilage content could absorb and block uptake of medication. It's a reasonable concern, and the precaution is probably warranted.
> It makes dosing difficult as I take most of my meds around meal times, and it says marshmallow should be taken with food.
>
> QI'd perhaps give it a quick trial, and see if it's of any benefit. If you don't notice improvement, it's probably not worth the effort to schedule everything around it.
Regards,
Lar
Posted by Larry Hoover on December 21, 2008, at 13:52:24
In reply to Re: GERD tangent » Larry Hoover, posted by Quintal on December 12, 2008, at 19:28:43
Medical concensus has been changing about the influence/interaction between GERD and Helicobacter pylori. I had the older perspective, and I want to correct what I posted earlier.
It has been found that Hp infection actually improves responsiveness to proton pump inhibitor drugs, probably due to chemicals released by the bacteria themselves, which have the effect of reducing acid rebound as the drug effect wanes between doses. It's not clear if antibiotic treatment is required to eradicate HP, either, as the PPI drugs also inhibit an essential biochemical pathway in the bacteria. So, perhaps the big issue is how the drug controls symptoms. Or not.
A second concern, though, may be more important. I earlier mentioned gastrin, the hormone that the body secretes that induces hydrochloric acid release into the stomach. Proton pump inhibitors lead to chronic hypergastrinaemia (high blood concentrations of gastrin), which is associated with a significantly increased risk of upper GI tract cancers, especially carcinoid and those of the stomach wall. The association is not proven, but primary (genetic) hypergastrinaemia is associated with neoplasm. It's possible that people just haven't been treated with these drugs for long enough, yet, for any such association to come to light.
Regards,
Lar
Posted by Quintal on December 25, 2008, at 8:15:18
In reply to Re: more GERD tangent » Quintal, posted by Larry Hoover on December 21, 2008, at 13:52:24
I haven't had time to write a reply.
Q
Posted by mcpw on October 29, 2009, at 3:47:57
In reply to serotonin and bone density, posted by Larry Hoover on December 6, 2008, at 9:05:43
Interesting to note the link with serotonin. There is a strong history of osteoporosis in my family and being a 61 year old male thought it wise to have a Dexa scan to check my status, Surprised to find that my hip score is 3.3 on Z scale. Very dense bones and perhaps explains why I have always had trouble floating in water! I have noted the possible link to the LPR5 gene though have no idea whether this is the link in my case.
However, I have suffered from chronic idiopathic urticaria most of my life which had a very strong diurnal pattern. I would wake up clear but would be covered within 5 minutes of waking up, even if I did not move, and would have a second attack in the evening. I always suspected it was triggered by a diurnally fluctuating hormone, serotonin being a strong suspect.
Has anyone come across a similar connection? Any suggestions?
This is the end of the thread.
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