Youthful Metabolism? Reduce Dietary Fat And Inhibit Serotonin

[jaa]

Just came across this CBC article in which researchers at McMaster are sounding quite like Peat.

http://www.cbc.ca/news/canada/hamilton/ ... -1.2862231

 

[Such_Saturation]

Obligatory

 

[haidut]

Just came across this CBC article in which researchers at McMaster are sounding quite like Peat.

http://www.cbc.ca/news/canada/hamilton/ ... -1.2862231

The important thing to note is that they found that inhibiting peripheral serotonin is the key to restoring metabolism. They claim that serotonin reduction in the brain has no effect or at least they think it would have no effect.
Here is the actual study, so if somebody has access to it and can check what chemical they used to inhibit TPH-1 that would be great.
http://www.nature.com/nm/journal/vaop/n ... .3766.html

Here is also a patent they filed to develop a new pill focused on just that goal.
http://www.google.com/patents/WO2014124523A1?cl=en

I am a bit confused though. The news articles says this:
"...Published in Nature Medicine Monday, researchers from McMaster University show that by inhibiting the hormone serotonin found in the gut of mice, the body's natural furnace, a lesser-known organ called brown adipose tissue, is more active and burns more calories."

However, the patent says this:
"...The method of claim 1 , wherein the compound targets peripheral serotonin other than serotonin in the gastrointestinal tract."

So, one place says it is the gut serotonin that need to be inhibited and the other says peripheral serotonin but not gut serotonin. However, that may be fine since the patent says this:
"...The method of claim 1, wherein the compound inhibits tryptophan hydroxylase 1 (TPH1)."

and also this:
'...The method of claim 9, wherein the serotonin receptor is selected from the group consisting of 5-HTla, 5-HTlb, 5-HT2b, 5-HT4 and 5-HT5a".

So, inhibiting TPH-1 or blocking the above serotonin receptors is the way to go. One way to do it is by taking vitamin D. Here is another thread I posted before where it shows that vitamin D does just that:
viewtopic.php?f=75&t=3300&hilit=vitamin+D+serotonin+gut+brain

However, I am not sure what the effective dosage would be. Based on the above listed serotonin receptors, it seems that ondansetron would not work as it targets the 5-HT3 receptor exclusively. However, you can block all of the above receptors with a combination of drugs like methysergide, lisuride, tegaserod, etc. Unfortunately, you'd have to take a handful of pills and some of these drugs are still experimental.
So, it seems that the best options right now are vitamin D (if we figure out the dosage), or TPH-1 inhibitors like this one:
http://www.dalton.com/prod_name/1040526-12-2.aspx

Finally, the good old diet trick with additional BCAA should also help but it would also potentially deplete brain serotonin too.
Very interesting stuff, and confirming Peat's views once again.
And for those interested in an overview of other methods for increasing metabolism, take a look at this:
http://ltc.nutes.ufrj.br/constructore/o ... 202007.pdf

Reference #46 of the above study claims that T3 can do a very good job of shedding fat WITHOUT losing muscle as well, but the side effects were greatly increased heart rate, which was viewed as bad.
http://press.endocrine.org/doi/abs/10.1210/en.2003-0973
Instead, the study above proposes a targeted chemical GC-1, which works on the thyroid "receptor" without affecting heart rate much.

 

[loess]

haidut, they used that experimental drug that you linked to (LP-533401), apparently originally developed and tested in humans as a treatment for irritable bowel syndrome, but more recently aimed at inhibiting gut-derived serotonin synthesis for the purpose of treating osteoporosis.

Full text of the study is attached to this post.

 

[jaa]

lol S_S. The strategy is foolproof. Sure you get depressed, but you're too weak to take any tragic measures so it's all good.

Thanks for that great reply and added context haidut! And nice find loess!

 

[haidut]

haidut, they used that experimental drug that you linked to (LP-533401), apparently originally developed and tested in humans as a treatment for irritable bowel syndrome, but more recently aimed at inhibiting gut-derived serotonin synthesis for the purpose of treating osteoporosis.

Full text of the study is attached to this post.

I posted a study months ago on the forum showing caffeine has very similar effects on bone to the LP drug. Since caffeine also lowers serotonin in plasma and increases metabolism, I wonder if it works similar to LP??
However, caffeine will raise heart rate in most people and I think this is what the scientists are trying to avoid.
Oh well, we will see how this evolves. For now, lowering serotonin with BCAA, charcoal and carrot seems to be the safer approach.

 

[Kasper]

Just one thought:

inhibiting gut serotonin --> increase brown fat cells
the iceman --> has much increased brown fat cells
cold showers --> increase brown fat cells

Could it be that cold showers actually lower gut serotonin. I understand, cold showers can get someone in a stress state, but if you go very slowly, from warm to cold, and are in general a good health, my experience is that it feels not stressy, but it feels very good. The highest body temperature that I've ever measured (37 degrees) was right after I did a cold shower. Like 2 mins, after a cold shower.

 

[Suikerbuik]

Interesting jaa, thanks!

So, it seems that the best options right now are vitamin D (if we figure out the dosage)

I'm afraid we don't get the vitamin D dose figured out. I am not going to repeat myself, but vitamin D suppletion does not indiscriminately mean increased VDR activity.

The study Haidut refers to in his post above (link) is talking about VDRE and vitamin D hormone. Or in other words 1,25D "activates" the vitamin D receptor and regulates gene expression by binding to vitamin D response elements (VDREs). You can find the data sets on which they build their hypothesis yourself here: http://press.endocrine.org/doi/suppl/10.1210/me.2005-0106. Table 1 focusses on gene expression/ repression and table 4 your can see those VDREs they are talking about.

To shortly reply on the IBS improvement that you suggest might be because of TPH1 repression. I think the complexity beyond understanding at this point in time since the vitamin D receptor influences the expression of at least 900 genes with many affecting the immune system. However serotonin may well be an interesting target, as this data set also shows us also that the HTR2C gene (5-hydroxytryptamine (serotonin) receptor 2C) is also highly influenced by vitamin D receptor activation (score 9.47, no. 8 on the list in order from high to low). Whether this means that it is upregulated or downregulated is unclear to me.

Sorry for going a bit off topic jaa. I'll shut up.

 

[Such_Saturation]

The showers increase your norephinephrine which directly turns on brown fat. I think serotonin, if it is necessary for hibernation (as is a cold stimulus), will also turn on the brown fat to provide the heat during the sleep. It is very context-dependent and gut serotonin might be a signal related to the presence of food, for instance. Decreased brown adipose tissue thermogenic activity following a reduction in brain serotonin by intraventricular p-chlorophenylalanine.http://www.ncbi.nlm.nih.gov/pubmed/2443195

 

[tara]

Just one thought:

inhibiting gut serotonin --> increase brown fat cells
the iceman --> has much increased brown fat cells
cold showers --> increase brown fat cells

Could it be that cold showers actually lower gut serotonin. I understand, cold showers can get someone in a stress state, but if you go very slowly, from warm to cold, and are in general a good health, my experience is that it feels not stressy, but it feels very good. The highest body temperature that I've ever measured (37 degrees) was right after I did a cold shower. Like 2 mins, after a cold shower.

I think Rakhimov's description of Buteyko method includes cold showers as helpful to metabolism when CP is 25s or higher, but counter-productive if CP < 25s. Could be differences in effect depending on BMR and temps?

 

[elbatero]

The important thing to note is that they found that inhibiting peripheral serotonin is the key to restoring metabolism. They claim that serotonin reduction in the brain has no effect or at least they think it would have no effect.
Here is the actual study, so if somebody has access to it and can check what chemical they used to inhibit TPH-1 that would be great.
http://www.nature.com/nm/journal/vaop/n ... .3766.html

Just thought I'd post this here as I was looking into this. I looked up the study and found they used this compound to chemically inhibit TPH-1. LP533401 hcl
The effect of an inhibitor of gut serotonin (LP533401) during the induction of periodontal disease. - PubMed - NCBI