MAO-B / Serotonin causes atherosclerosis, Selegiline treats

[Mauritio]

Research on Selegiline seems to be picking up and researchers are now using it for all kinds of disorders like fatty liver disease or atherosclerosis, not just Parkinson's and anti-aging.

This study looked the causes of atherosclerosis and if MAO-B has something to do with it. It turned it, it does.
MAO-B causes oxidative stress in the blood vessels, which is central to atherosclerosis. Selegiline was able to reduce those inflammatory markers, by working as an antioxidant.
They noticed that simply putting the animals on a high fat diet was enough to cause the increase in MAO-B and ROS.
I suspect the high fat diet, was also a high PUFA diet, since the MDA levels were increased, which is normally caused by a high PUFA diet, so it looks like PUFA can increase MAO-B and thus serotonin on its own.

They also did an in vivo study showing that selegiline, in normal human doses, can ameliorate atherosclerosis.
They also showed that this amelioration was downstream from a change in the microbiome: Selegiline increased a few beneficial bacterial genera like Akkermansia, which has a lot of its own pro-metabolic effects ( A. Muciniphila Improves Insulin Sensitivity, Lowers Weight+ Cholesterol+reduces Endotoxin Load) and decreased even more some pathological genera.

Here you can see that selegiline decreased total bacteria genera a lot more than the number it increased, so I presume that the total bacteria number went down. Interestingly the bacterium genus that decreased the most was Clostridia. The study about serotonin I quote below shows that Clostridia is among the top serotonin producers in the gut. Reducing clostridia and another genus, lowered serotonin production in the gut by as much as 50%!
" ...in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao's team raised mice without the bacteria, more than 50% of their gut serotonin was missing."

What I found interesting as well, is that animals on a HFD, had zero Akkermansia bacteria in their gut, just after starting Selegiline they increased, which can be seen here:

So, Selegiline was able to alter the gut microbiome, who would have thought?
Although the effect on the atherosclerosis is downstream of the change in the microbiome, I suspect that the effect on the microbiome is downstream from a reduction in serotonin (through MAO-B inhibition): I posted a study years ago on how serotonin itself can alter the microbiome (Serotonin Itself Alters The Microbiome, Central Role Of Only 2 Bacteria Species) so this might be the root of all evil once again.

- Inhibition of MAOB Ameliorated High-Fat-Diet-Induced Atherosclerosis by Inhibiting Endothelial Dysfunction and Modulating Gut Microbiota

 

[Mauritio]

Here is another study, also from this year, that comes to the same conclusion: Inhibition of monoamine oxidase B reduces atherosclerosis and fatty liver in mice - PubMed .

"Inhibition of MAO B (by deprenyl), but not MAO A (by clorgyline), reduced the atheroma area in the thoracic aorta and aortic sinus in ApoE-deficient mice fed the cholesterol-enriched diet for 15 weeks. MAO B inhibition attenuated oxidative stress, expression of adhesion molecules, production of inflammatory cytokines, and macrophage infiltration in atherosclerotic plaques and decreased plasma triglyceride and low-density lipoprotein (LDL) cholesterol concentrations."

Again Selegiline was strikingly effective at preventing ROS, in this case it even lowered ROS levels to below control levels

Selegiline was also very effective at decreasing the lipid droplet area in the liver, which is a major factor in NAFLD and hepatic steatosis.

- Inhibition of monoamine oxidase B reduces atherosclerosis and fatty liver in mice - PubMed

 

[TheCodez]

Too bad selegiline shows positive for amphetamine use on a drug test. ;-(

 

[Pete Rey]

Synchronicity. Received the package last week and eyeballed my first 1mg crumb this morning. There is that familiar feeling from the amphetamine metabolites to ADHD meds which I normally wouldn't be using. Certainly doesn't feel bad. We'll see if there's any crash this evening or tomorrow. Never really planned on touching a stimulant other than coffee again. But, the hype seems to be real. I plan on spacing the dosing out by a few days for a bit, and depending on how that goes maybe try daily dosing.

 

[Mauritio]

Too bad selegiline shows positive for amphetamine use on a drug test. ;-(

Is that also the case when you take it sublingually ?

Synchronicity. Received the package last week and eyeballed my first 1mg crumb this morning. There is that familiar feeling from the amphetamine metabolites to ADHD meds which I normally wouldn't be using. Certainly doesn't feel bad. We'll see if there's any crash this evening or tomorrow. Never really planned on touching a stimulant other than coffee again. But, the hype seems to be real. I plan on spacing the dosing out by a few days for a bit, and depending on how that goes maybe try daily dosing.

1mg sublingually? I take 1.25mg sublingually once a week. Feels great on every front, maybe a bit anxious sometimes but not a lot.
There is not crash because selegiline actually raises your dopamine baseline and doesnt just release dopamine like normal stimulants, I posted a study on that somewhere. UNLESS you take a microdose, which I did once and it felt like I'm on cocaine and there was a huge crash the next day.

 

[Validus]

Is that also the case when you take it sublingually ?

1mg sublingually? I take 1.25mg sublingually once a week. Feels great on every front, maybe a bit anxious sometimes but not a lot.
There is not crash because selegiline actually raises your dopamine baseline and doesnt just release dopamine like normal stimulants, I posted a study on that somewhere. UNLESS you take a microdose, which I did once and it felt like I'm on cocaine and there was a huge crash the next day.

Very interesting! The dose used in the study was quite a bit higher than your 1.25 mg sublingual once per week though.

Essentially, you'd need to be taking about 5 mg's every other day to match the protocol used with these mice.

"Mice received selegiline (MedChemExpress, Shanghai, China) at a dose of 0.6 mg/kg body weight every other day for 6 weeks by intraperitoneal injection (i.p.) after a 10-week exposure to ND or HFD feeding. The dose of selegiline was selected based upon one previous report [17], and the calculation from a simple practice guide for dose conversion between mice and human [18]. The oral dose of selegiline used in the human therapy is 5–10 mg/day [19]."

 

[Wayne J]

Research on Selegiline seems to be picking up and researchers are now using it for all kinds of disorders like fatty liver disease or atherosclerosis, not just Parkinson's and anti-aging.

This study looked the causes of atherosclerosis and if MAO-B has something to do with it. It turned it, it does.
MAO-B causes oxidative stress in the blood vessels, which is central to atherosclerosis. Selegiline was able to reduce those inflammatory markers, by working as an antioxidant.
They noticed that simply putting the animals on a high fat diet was enough to cause the increase in MAO-B and ROS.
I suspect the high fat diet, was also a high PUFA diet, since the MDA levels were increased, which is normally caused by a high PUFA diet, so it looks like PUFA can increase MAO-B and thus serotonin on its own.

They also did an in vivo study showing that selegiline, in normal human doses, can ameliorate atherosclerosis.
They also showed that this amelioration was downstream from a change in the microbiome: Selegiline increased a few beneficial bacterial genera like Akkermansia, which has a lot of its own pro-metabolic effects ( A. Muciniphila Improves Insulin Sensitivity, Lowers Weight+ Cholesterol+reduces Endotoxin Load) and decreased even more some pathological genera.

Here you can see that selegiline decreased total bacteria genera a lot more than the number it increased, so I presume that the total bacteria number went down. Interestingly the bacterium genus that decreased the most was Clostridia. The study about serotonin I quote below shows that Clostridia is among the top serotonin producers in the gut. Reducing clostridia and another genus, lowered serotonin production in the gut by as much as 50%!
" ...in mice, a specific mixture of bacteria, consisting mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to gut cells to increase production of serotonin. When Hsiao's team raised mice without the bacteria, more than 50% of their gut serotonin was missing."
View attachment 57884

What I found interesting as well, is that animals on a HFD, had zero Akkermansia bacteria in their gut, just after starting Selegiline they increased, which can be seen here:
View attachment 57885

So, Selegiline was able to alter the gut microbiome, who would have thought?
Although the effect on the atherosclerosis is downstream of the change in the microbiome, I suspect that the effect on the microbiome is downstream from a reduction in serotonin (through MAO-B inhibition): I posted a study years ago on how serotonin itself can alter the microbiome (Serotonin Itself Alters The Microbiome, Central Role Of Only 2 Bacteria Species) so this might be the root of all evil once again.

- Inhibition of MAOB Ameliorated High-Fat-Diet-Induced Atherosclerosis by Inhibiting Endothelial Dysfunction and Modulating Gut Microbiota

However from Selegiline Uses, Side Effects & Warnings
Selegiline may cause serious side effects. Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• trouble breathing;
• confusion, hallucinations, unusual thoughts or behavior;
• increased tremors or uncontrolled muscle movements;
• worsening side effects of your other medications;
• high levels of serotonin in the body (when taken with an antidepressant)--agitation, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting; or
• dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, anxiety, nausea, vomiting, severe chest pain, shortness of breath, pounding heartbeats, or seizure (convulsions).

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking selegiline. Talk with your doctor if this occurs.

 

[youngsinatra]

.

 

[Pete Rey]

However from Selegiline Uses, Side Effects & Warnings
Selegiline may cause serious side effects. Call your doctor at once if you have:

• a light-headed feeling, like you might pass out;
• trouble breathing;
• confusion, hallucinations, unusual thoughts or behavior;
• increased tremors or uncontrolled muscle movements;
• worsening side effects of your other medications;
• high levels of serotonin in the body (when taken with an antidepressant)--agitation, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting; or
• dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, anxiety, nausea, vomiting, severe chest pain, shortness of breath, pounding heartbeats, or seizure (convulsions).

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking selegiline. Talk with your doctor if this occurs.

This is called legally covering your **** so as not to get sued. Everyone here is being more than responsible.

Is that also the case when you take it sublingually ?

1mg sublingually? I take 1.25mg sublingually once a week. Feels great on every front, maybe a bit anxious sometimes but not a lot.
There is not crash because selegiline actually raises your dopamine baseline and doesnt just release dopamine like normal stimulants, I posted a study on that somewhere. UNLESS you take a microdose, which I did once and it felt like I'm on cocaine and there was a huge crash the next day.

I read your post and recall reading that kind of experience reported before elsewhere regarding microdosing amphetamines. I just tend to be sensitive to stimulants, especially comedown/rebound effects, so that's what I'm monitoring for. I'm interested in the pro-metabolic effects but not at the expense of riding a rollercoaster of ups and downs. Slept well and feel pretty normal today which is a good sign. Maybe a tiny bit tired but nothing out of the ordinary.

 

[Wayne J]

This is called legally covering your **** so as not to get sued. Everyone here is being more than responsible.


I read your post and recall reading that kind of experience reported before elsewhere regarding microdosing amphetamines. I just tend to be sensitive to stimulants, especially comedown/rebound effects, so that's what I'm monitoring for. I'm interested in the pro-metabolic effects but not at the expense of riding a rollercoaster of ups and downs. Slept well and feel pretty normal today which is a good sign. Maybe a tiny bit tired but nothing out of the ordinary.

Appreciate the reply - really interested in reducing plaque buildup. A CT scan shows 'severe blockage' in upper right artery and lower left venial structure' - but that was from one angle chest scan while at Mayo that was for lung. Going back next week for a full scan and workup - and am dreading the laundry list of meds they will want to ush on me.
Have been using something called Cavadex (enema insertion of cyclodextrin) from Australia for about 4 weeks. Hoping it reduces some of the plaque that I wont ned stents or whatever.
No Angina signs even getting heart rate up to 135 - BPs are normal to slightly high (138/75) - so sucking down anything provent to reduce plaque.
Thanks for the reply!

 

[Mauritio]

Very interesting! The dose used in the study was quite a bit higher than your 1.25 mg sublingual once per week though.

Essentially, you'd need to be taking about 5 mg's every other day to match the protocol used with these mice.

"Mice received selegiline (MedChemExpress, Shanghai, China) at a dose of 0.6 mg/kg body weight every other day for 6 weeks by intraperitoneal injection (i.p.) after a 10-week exposure to ND or HFD feeding. The dose of selegiline was selected based upon one previous report [17], and the calculation from a simple practice guide for dose conversion between mice and human [18]. The oral dose of selegiline used in the human therapy is 5–10 mg/day [19]."

There is a study showing several times increased blood levels using subingual admin, so the dose is spot on, not the once a week part of course.

 

[Mauritio]

This is called legally covering your **** so as not to get sued. Everyone here is being more than responsible.


I read your post and recall reading that kind of experience reported before elsewhere regarding microdosing amphetamines. I just tend to be sensitive to stimulants, especially comedown/rebound effects, so that's what I'm monitoring for. I'm interested in the pro-metabolic effects but not at the expense of riding a rollercoaster of ups and downs. Slept well and feel pretty normal today which is a good sign. Maybe a tiny bit tired but nothing out of the ordinary.

Good to know. For me it also doesn't cause any hangover or similar things. Maybe it's a bit harder to fal asleep some of the time, but nothing a little magnesium and honey cant handle.