Endotoxin (LPS) May Cause Depression / Anhedonia

[Lizb]

Benadryl is often mentioned on the forum but isn't it know as an anticholinergic, thus dementia causing drug?

 

[yerrag]

Benadryl is often mentioned on the forum but isn't it know as an anticholinergic, thus dementia causing drug?

I'm not aware of the effect on dementia, but I also know cyproheptadine is anticholinergic as well.

I had planned on using cyproheptadine on my mom hoping it would help restore her urinary bladder control, as this is a function frequently lost in old age. I think it had to do with muscles being too relaxed when the cholinergic system becomes too dominant. I suppose if one takes too much anticholinergics, there would be an imbalance of. another sort.

Last night, I couldn't sleep just on benadryl alone. I rubbed 3 drops of cyproheptadine and I fell asleep. I'm not sure if I should take this to mean that I'm still high on serotonin.

 

[Lizb]

I'm not aware of the effect on dementia, but I also know cyproheptadine is anticholinergic as well.

I had planned on using cyproheptadine on my mom hoping it would help restore her urinary bladder control, as this is a function frequently lost in old age. I think it had to do with muscles being too relaxed when the cholinergic system becomes too dominant. I suppose if one takes too much anticholinergics, there would be an imbalance of. another sort.

Last night, I couldn't sleep just on benadryl alone. I rubbed 3 drops of cyproheptadine and I fell asleep. I'm not sure if I should take this to mean that I'm still high on serotonin.

A family member has been taking medication for bladder control and has since begun to show signs of dementia, very sad. He has now been taken off the medication to see if any improvement can be made. Although a known side effect it does not appear on the patient data sheet that comes with the medication - outrageous.

I then discovered this:-


Common anticholinergic drugs like Benadryl linked to increased dementia risk. ... In a report published in JAMA Internal Medicine, researchers offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia. Anticholinergic drugs block the action of acetylcholine


I was wondering whether the use of a TENS machine or red light might help to control that urgent bladder. I have also downloaded a set of exercises for this condition fromthe Nutritious Movement website.

I hope your mother gets the control to give her confidence. It's a real confidence knock and in my e perience restricts where you are prepared to go.

All the best.

 

[yerrag]

A family member has been taking medication for bladder control and has since begun to show signs of dementia, very sad. He has now been taken off the medication to see if any improvement can be made. Although a known side effect it does not appear on the patient data sheet that comes with the medication - outrageous.

I then discovered this:-


Common anticholinergic drugs like Benadryl linked to increased dementia risk. ... In a report published in JAMA Internal Medicine, researchers offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia. Anticholinergic drugs block the action of acetylcholine


I was wondering whether the use of a TENS machine or red light might help to control that urgent bladder. I have also downloaded a set of exercises for this condition fromthe Nutritious Movement website.

I hope your mother gets the control to give her confidence. It's a real confidence knock and in my e perience restricts where you are prepared to go.

All the best.

A family member has been taking medication for bladder control and has since begun to show signs of dementia, very sad. He has now been taken off the medication to see if any improvement can be made. Although a known side effect it does not appear on the patient data sheet that comes with the medication - outrageous.

I then discovered this:-


Common anticholinergic drugs like Benadryl linked to increased dementia risk. ... In a report published in JAMA Internal Medicine, researchers offers compelling evidence of a link between long-term use of anticholinergic medications like Benadryl and dementia. Anticholinergic drugs block the action of acetylcholine


I was wondering whether the use of a TENS machine or red light might help to control that urgent bladder. I have also downloaded a set of exercises for this condition fromthe Nutritious Movement website.

I hope your mother gets the control to give her confidence. It's a real confidence knock and in my e perience restricts where you are prepared to go.

All the best.

Thanks for the well wishes. I should have mentioned that I would have used Cyproheptadine on my mom except that her passing two years ago was the reason I didn't get the chance to use it on her. Speaking of bladder control, my parents' experience has been that it was the use of fluoroquinolone antibiotics like Cipro and Levofloxocin (or Levaquin) to fight UTI that contributed not only to dementia, but to a general loss of nerve control. Even their ability to control their throat muscles for chewing, referred to by doctors as their sensorium, was affected.

The use of anticholinergics may just be incidental to dementia, given how mainstream research often ascribes causality faultily in order to absolve a party or a heavily marketed substance of any blame. Or it may be a case of using an unrealistically heavy dosage of anticholinergics on a study intended to give a foregone negative conclusion on anticholinergics. We also have to be cognizant of Paracelsius' statement that the poison is in the dosage.

Not to say the study is wrong (as I haven't read it), but I'm just leery of studies as many are based on methodologies, analyses, and conclusions derived that need to be examined and critiqued.

n.b. I failed to mention that I believe that in both my parents' case, I wished I knew how bad fluoroquinolone antibiotics were as I now believe they had a lot to do with their dementia.

 

[Lizb]

Thanks for the well wishes. I should have mentioned that I would have used Cyproheptadine on my mom except that her passing two years ago was the reason I didn't get the chance to use it on her. Speaking of bladder control, my parents' experience has been that it was the use of fluoroquinolone antibiotics like Cipro and Levofloxocin (or Levaquin) to fight UTI that contributed not only to dementia, but to a general loss of nerve control. Even their ability to control their throat muscles for chewing, referred to by doctors as their sensorium, was affected.

The use of anticholinergics may just be incidental to dementia, given how mainstream research often ascribes causality faultily in order to absolve a party or a heavily marketed substance of any blame. Or it may be a case of using an unrealistically heavy dosage of anticholinergics on a study intended to give a foregone negative conclusion on anticholinergics. We also have to be cognizant of Paracelsius' statement that the poison is in the dosage.

Not to say the study is wrong (as I haven't read it), but I'm just leery of studies as many are based on methodologies, analyses, and conclusions derived that need to be examined and critiqued.

n.b. I failed to mention that I believe that in both my parents' case, I wished I knew how bad fluoroquinolone antibiotics were as I now believe they had a lot to do with their dementia.

I am sorry to hear that.
Thank you all that and I'll write that down. We have a battle ahead now to try and stem this damn dementia, if that's what it is, (in the middle of diagnosis) and the bladder issue. Thank you again.

 

[yerrag]

I am sorry to hear that.
Thank you all that and I'll write that down. We have a battle ahead now to try and stem this damn dementia, if that's what it is, (in the middle of diagnosis) and the bladder issue. Thank you again.

I wish you well in your efforts to stem dementia with your family member. I think another approach is to somehow control factors that trigger urination. I find that acidic urine, a consequence of acid blood/ecf, triggers the urge to urinate even wheb bladder isn't full. That was from my own experience. Another thing is high endotoxin load, which may come from the intestines into the blood, or from periodontal infection into the blood, or in my ongoing experience, from the lysing of plaque harboring endotoxins and bacteria, as well as from antibiotic adminstration where endotoxin is released from bacterial die-off ( aka herxheimer reaction).

RF signals such as wifi, in my experience, has also triggered urination at night.

Every little bit helps. Good luck!

 

[Pointless]

@Lizb here Ray Peat summarizes the reasoning for linking anticholinergics with dementia and why it's faulty.

New Page Title Here

 

[Lizb]

I wish you well in your efforts to stem dementia with your family member. I think another approach is to somehow control factors that trigger urination. I find that acidic urine, a consequence of acid blood/ecf, triggers the urge to urinate even wheb bladder isn't full. That was from my own experience. Another thing is high endotoxin load, which may come from the intestines into the blood, or from periodontal infection into the blood, or in my ongoing experience, from the lysing of plaque harboring endotoxins and bacteria, as well as from antibiotic adminstration where endotoxin is released from bacterial die-off ( aka herxheimer reaction).

RF signals such as wifi, in my experience, has also triggered urination at night.

Every little bit helps. Good luck!

I have just convinced him to start carrot salad. Thank you for all that and all well noted. It feels very supportive. Most useful!

 

[Lizb]

@Lizb here Ray Peat summarizes the reasoning for linking anticholinergics with dementia and why it's faulty.

New Page Title Here

Thank you. I'll read that.

 

[Sativa]

Endotoxin itself is an aromatase activator

Likely, the Depression/Anhedonia from endotoxin is encouraged by increased estrogen levels, as well as activation of TLR4.

 

[Xemnoraq]

As many readers know, anhedonia is one of the most pernicious aspects of clinical depression. It is present in other mental health conditions but is most pronounced and severe in clinical unipolar depression. It is also especially resistant to treatment and many doctors simply accept it as something that current drugs cannot address and focus on improving overall quality of life for the patient as much as current pharma options allow. The sad reality is that despite the well-known link between anhedonia and low dopamine (and thus high-serotonin), nobody has made the suggestion (at last officially) that serotonin may actually be a cause of depression. No suggestions have been made about treating anhedonia with dopamine agonists and/or serotonin antagonists despite the mountain of evidence from animal studies.
Be that as it may, the study below demonstrates the endotoxin can directly cause depression and anhedonia, by acting on the TLR receptors and thus increasing inflammation. While the study does not mention it, this also directly implicates serotonin as a causal factor in depression as endotoxin manifests most of its negative effects on health by activating serotonin synthesis in the gut and by increasing NO synthesis/release. It is impossible to activate the TLR4 receptors the study below discusses without also increasing serotonin/NO. I suppose it would be too brave for the authors to call serotonin out for what it is, but at the very least the role of endotoxin in chronic conditions is starting to get recognized, and I'd take this as a good start. The study does claim that the anhedonic and depressive effects of endotoxin affect mostly females, but I am not convinced males are exempt. I think males are simply more resilient initially due to their higher testosterone levels, which itself has potent antidepressant effects. On the other hand, the higher estrogen levels in women predispose to depression and females' estrogen levels are more sensitive to endotoxin assaults. This likely explains the gender differences seen in the studies, and when these differences between genders dwindle in older age, endotoxin becomes just as strong depressive and anhedonic agent for males as well. As such, blocking TLR4 may be a viable treatment for anhedonia/depression and studies with TLR4 antagonists like naltrexone, amitriptyline, cyproheptadine, progesterone, vitamin D/A, riboflavin, have all demonstrated antidepressant effects further corroborating the findings of the study below.

Sex Differences in the Relationship Between Inflammation and Reward Sensitivity: A Randomized Controlled Trial of Endotoxin - ScienceDirect
Brain study may explain why depression is more common in women

"...Anhedonia is one of the hallmarks of major depressive disorder. Anhedonia describes the inability to derive joy or pleasure from activities that used to feel enjoyable. On a neurological level, anhedonia presents itself as reduced activity in the brain's reward processing area, called the ventral striatum."

"...Prof. Eisenberger and colleagues administered either a low dose of an endotoxin — in order to induce inflammation — or a placebo to depression-free men and women. In total, the study included 115 participants, 69 of whom were female. The researchers randomly assigned the participants to either the control/placebo group or the low-dose endotoxin group."

"...The results revealed that the endotoxin reduced the activity of the reward-processing ventral striatum. However, the researchers noticed that this effect differed according to sex. "Specifically," report Prof. Eisenberger and colleagues, "in female participants, endotoxin (vs. placebo) led to decreased [ventral striatum] activity in anticipation of reward, but this effect was not present in male participants." Also, these decreases in the activity of the ventral striatum "were related to increases in inflammation for female but not male participants."

Do you think its possible for progesterone
(in high enough doses) to cause this in makes due to its anti-androgenic testosterone effect?

Ive been using reasonably higher doses of progesterone sometimes paired with pregnenolone DHEA but the progesterone is more constant and higher doses and ive notcied its made my cortisol plummet which is great! But ive noticed this sort of long overhanging gloom over my head lately feels like a lack of dopamine and i find myself sleeping all the time, im speculating in may be connected,

I think its definetly the endotoxin behind it all because i have chronic issues with that however it seems i respond differently to endotoxin while using progesterone, i find i respond way better in the sense of no cortisol spikes, but just this constant fatigue and sort of melancholy state

 

[Mr Joe]

There are multiple reports of forum users experiencing this actually, even from low doses. Several women reported this from 2mg daily. I seem to remember either @Blossom or @thebigpeatowski were some who had those side effects. I also got (mildly) elevated liver enzymes when I was using 8mg-12mg cypro daily back in my early Peat days when I had high cortisol/prolactin. And yes, my liver enzymes were normal before starting cypro. It does not happen in everybody, that's why I suggested starting low, testing liver and everything seems fine then maybe increasing the dose. Finally, several people asked Peat over email about potential liver issues with cypro and he told them it may cause issues with BOTH gallbladder and liver. I think those emails are also posted here somewhere. But in typical Peat fashion, he has told different things to others including the latest statement that cypro is safe even in high doses. Maybe he does not consider the enzyme elevation to be clinically relevant??
Cyproheptadine
Cyproheptadine-Induced Acute Liver Failure
(PDF) Cyproheptadine for central hypertension?

Here is one email he sent to a person who was concerned about 4mg cypro changing a male's urine color almost immediately.

"RP: ...Large amounts of cyproheptadine might affect the gallbladder or ducts in a way that could increase bilirubin, making the urine brown. I have found that less than one milligram of it can be very helpful; I think it should be taken for only a few days at a time. Thyroid, progesterone, and maybe small amounts of DHEA or testosterone (around 2 to 4 mg/day) should help to reduce inflammation, improve immunity and normalize the ureters."

@haidut thank you for that. You said somewhere that for a patient trying to fix things such as gut issues or high cortisol/prolactin, high dose cypro (>16 mg) could be an approach. Would you think that adding 500 mg Niacinamide (or K2?) could prevent liver enzymes and/or gallbladder ?