Huperzine, Choline, and Cognition

[DixieWrecked]

Huperzine-a increases levels of acetylcholine in the brain by inhibiting acetyltransferase. There are currently several Rx acetyltransferase inhibitors that are used to treat dementia and Alzheimer's. I know that some feel there is a bit of brain fog that comes with TRT and I was curious if anyone has deployed this compound and if it was successful in improving cognitive function. I am on day three of my trial and so far haven't noticed too much, maybe a tad better word recall. I will keep everyone posted but would love to have a thread with choline related discussion.

 

[sammmy]

I sometimes take Huperzine to help me reaching orgasm but I do not feel well on it and do not like it. I am not on TRT.

Be very careful not to overdose on Huperzine. Side effects range from a headache, nausea, insomnia to much worse as vomiting, "cholinergic crisis", respiratory failure etc.

AChE inhibitors like Huperzine are unpleasant drugs with a narrow therapeutic interval. Some poisons like Sarin gas or snake poisons are exactly that.

The treatment of "brain fog" would depend on the cause - typically problem with blood circulation in the brain leading to a lack of oxygenation. Traditional thing to try for that is Gingko Biloba.

 

[Nelson Vergel]

Brain fog's main causes are high blood pressure (it could be caused by TRT-related water retention and/or high hematocrit), sleep apnea, or a side effect from a medication.

 

[DixieWrecked]

One of the main reasons I am looking at it is because Alzheimer's runs on my dad's side of the family. My grandpa didn't make it past 60. My uncle made it to 73 and my dad is about to pass at the age of 73. All from Alzheimer's. When I notice my memory slip or my words not coming easy I get paranoid. The Dr said my dad most likely started going downhill when he was around 40. I just turned 40.

 

[Nelson Vergel]

This works for me but I only take once or twice per week since I have noticed low mood the day after. I take it when i have a lot of work. My mom has Alzeimers, so I know what you mean.

Has Anyone Used Alpha-GPC ?

Has anyone used this supplement? Oral supplementation of alpha-GPC is of interest for nootropic purposes, as it appears to have cognitive-enhancing properties (no human evidence exists to support this in otherwise-healthy youth, but it does have support in rodents) and attenuate the rate of...

www.excelmale.com

 

[Graham]

I like phosphatidylserine

 

[sammmy]

There is a correlation between usage of NSAIDs and a lower incidence of Alzheimer. However that doesn't prove cause and effect - people tending to use NSAIDs may be less prone to Alzheimer for other reasons, not due to the NSAIDs:

Anti-inflammatory drugs and risk of Alzheimer's disease: an updated systematic review and meta-analysis

On a similar note, use of ibuprofen is correlated with a lower risk for Parkinson disease. No such correlation exists for the other NSAIDs. This was again a correlation study which does not prove a cause and effect, HOWEVER the higher the ibuprofen dose, the lower was the Parkinson's risk, which is suggesting of a cause and effect:

Use of ibuprofen and risk of Parkinson disease

 

[Cataceous]

One of the main reasons I am looking at it is because Alzheimer's runs on my dad's side of the family. ...

I have a genetic predisposition, though at least it doesn't seem to run in my family. I take an interest in things that might help. In addition to GPC and PS:

Selegiline—“The monoamine oxidase-B inhibitor L-deprenyl (Selegiline) is effective in treating Parkinson’s disease and possibly Alzheimer’s disease. The neuroprotective property of L-deprenyl may be unrelated to the inhibition of monoamine oxidase-B. Since nitric oxide (NO) modulates activities including cerebral blood flow and memory, we examined the effect of L-deprenyl on NO. L-Deprenyl induced rapid increases in NO production in brain tissue and cerebral vessels. Vasodilation was produced by endothelial NO- dependent as well as NO-independent mechanisms in cerebral vessels. The drug also protected the vascular endothelium from the toxic effects of amyloid-beta peptide. These novel actions of selegiline may protect neurons from ischemic or oxidative damage and suggest new therapeutic applications for L- deprenyl in vascular and neurodegenerative diseases.”

Selegiline HCL | JuicedMuscle.com

www.juicedmuscle.com

PDE5 inhibitor—“Specifically, various rodent studies have reported that PDE5 inhibitors can reverse cognitive impairments and pathology in aged wild-type mice and transgenic Alzheimer’s mouse models through mechanisms including reduced tau hyperphosphorylation (via GSK3β activation), increased BDNF, anti- inflammatory action, increased pCREB signaling, and reduced apoptosis and cell death [2; 3; 4; 5]. Beta- amyloid pathology has been reversed in some [3; 6] but not all [2; 5] studies.

“Whether these effects will occur in humans has yet to be tested. No human studies, observational or randomized, have examined if the use of PDE5 inhibitors can protect against dementia or brain aging.”

https://www.alzdiscovery.org/uploads/cognitive_vitality_media/PDE5-inhibitors-Cognitive-Vitality-For-Researchers.pdf

Lithium—“One study found that long-term lithium exposure from drinking water may be associated with a lower risk of being diagnosed with dementia. … One epidemiological study in Texas revealed that rates of death from Alzheimer’s were higher in areas with low levels of lithium in the water. In one clinical study, a micro-dose of just 300 mcg of lithium daily was found to significantly decrease cognitive decline in Alzheimer’s patients, compared to a placebo.”

How Does Lithium Work In The Brain? - Life Extension

Lithium may slow degenerative processes by inhibiting an age-accelerating enzyme in the brain and other organs.

www.lifeextension.com

Palmitoylethanolamide—(One of two PEAs) “Either preclinical or clinical studies indicate that PEA is potentially useful in a wide range of therapeutic areas, including eczema, pain, and neurodegeneration. … In the present review, we summarized the current preclinical and clinical evidence of PEA as a possible therapeutic agent in Alzheimer's disease. The possible PEA neuroprotective mechanism(s) of action is also described.”

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease - PubMed

<span><i>N</i>-Palmitoylethanolamide (PEA) is a non-endocannabinoid lipid mediator belonging to the class of the <i>N</i>-acylethanolamine phospolipids and was firstly isolated from soy lecithin, egg yolk, and peanut meal. Either preclinical or clinical studies indicate that PEA is potentially...

pubmed.ncbi.nlm.nih.gov

"Palmitoylethanolamide protects against the amyloid-β25-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease"

Palmitoylethanolamide Protects Against the Amyloid-β25-35-Induced Learning and Memory Impairment in Mice, an Experimental Model of Alzheimer Disease - PMC

Alzheimer disease (AD) is the most common form of neurodegenerative dementia. Amyloid-β deposition, neurofibrillary tangle formation, and neuro-inflammation are the major pathogenic mechanisms that in concert lead to memory dysfunction and decline ...

www.ncbi.nlm.nih.gov

Vascular dementia and aliamides: A new approach for the future

Vascular dementia and aliamides: A new approach for the future

OA Text is an independent open-access scientific publisher showcases innovative research and ideas aimed at improving health by linking research and practice to the benefit of society.

www.oatext.com

DHEA
Pregnenolone
“Pregnenolone sulfate and DHEA sulfate have also been found to improve cognition in animal studies[111][112][113][114][115][116][117][118]. In an animal model of b amyloid-induced amnesia, DHEA, DHEA sulfate, and pregnenolone sulfate attenuated amnesia in a dose-dependent manner[119]. Interestingly, inhibition of the steroid sulfatase enzyme improved the antiamnesic effect of DHEA sulfate[120][121], indicating that preventing neuroactive steroids from being converted out of their sulfate form may improve cognition.

“Nevertheless, the non-sulfated form of pregnenolone has been shown to improve cognition[122][123] and function[124][125] in schizophrenics. Schizophrenia is characterized by elevations in DHEA and DHEA sulfate and decreases in allopregnanolone, though it is yet unknown how pregnenolone is exerting its effect[126]. It was observed that changes in plasma steroid levels of pregnenolone and allopregnanolone correlated with functional improvements. Interestingly, studies indicate pregnenolone produces biphasic results, where lower dosed (30 mg/day) treatments produced better outcomes than higher dosed treatments (200 mg/day).”

The Power of Neuroactive Steroids

This article introduces the reader to the biosynthesis of neuroactive hormones and reviews what we know about their effects on cognition.

www.leoandlongevity.com

 

[DixieWrecked]

I have a genetic predisposition, though at least it doesn't seem to run in my family. I take an interest in things that might help. In addition to GPC and PS:

Selegiline—“The monoamine oxidase-B inhibitor L-deprenyl (Selegiline) is effective in treating Parkinson’s disease and possibly Alzheimer’s disease. The neuroprotective property of L-deprenyl may be unrelated to the inhibition of monoamine oxidase-B. Since nitric oxide (NO) modulates activities including cerebral blood flow and memory, we examined the effect of L-deprenyl on NO. L-Deprenyl induced rapid increases in NO production in brain tissue and cerebral vessels. Vasodilation was produced by endothelial NO- dependent as well as NO-independent mechanisms in cerebral vessels. The drug also protected the vascular endothelium from the toxic effects of amyloid-beta peptide. These novel actions of selegiline may protect neurons from ischemic or oxidative damage and suggest new therapeutic applications for L- deprenyl in vascular and neurodegenerative diseases.”

Selegiline HCL | JuicedMuscle.com

www.juicedmuscle.com

PDE5 inhibitor—“Specifically, various rodent studies have reported that PDE5 inhibitors can reverse cognitive impairments and pathology in aged wild-type mice and transgenic Alzheimer’s mouse models through mechanisms including reduced tau hyperphosphorylation (via GSK3β activation), increased BDNF, anti- inflammatory action, increased pCREB signaling, and reduced apoptosis and cell death [2; 3; 4; 5]. Beta- amyloid pathology has been reversed in some [3; 6] but not all [2; 5] studies.

“Whether these effects will occur in humans has yet to be tested. No human studies, observational or randomized, have examined if the use of PDE5 inhibitors can protect against dementia or brain aging.”

https://www.alzdiscovery.org/uploads/cognitive_vitality_media/PDE5-inhibitors-Cognitive-Vitality-For-Researchers.pdf

Lithium—“One study found that long-term lithium exposure from drinking water may be associated with a lower risk of being diagnosed with dementia. … One epidemiological study in Texas revealed that rates of death from Alzheimer’s were higher in areas with low levels of lithium in the water. In one clinical study, a micro-dose of just 300 mcg of lithium daily was found to significantly decrease cognitive decline in Alzheimer’s patients, compared to a placebo.”

How Does Lithium Work In The Brain? - Life Extension

Lithium may slow degenerative processes by inhibiting an age-accelerating enzyme in the brain and other organs.

www.lifeextension.com

Palmitoylethanolamide—(One of two PEAs) “Either preclinical or clinical studies indicate that PEA is potentially useful in a wide range of therapeutic areas, including eczema, pain, and neurodegeneration. … In the present review, we summarized the current preclinical and clinical evidence of PEA as a possible therapeutic agent in Alzheimer's disease. The possible PEA neuroprotective mechanism(s) of action is also described.”

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer's Disease - PubMed

<span><i>N</i>-Palmitoylethanolamide (PEA) is a non-endocannabinoid lipid mediator belonging to the class of the <i>N</i>-acylethanolamine phospolipids and was firstly isolated from soy lecithin, egg yolk, and peanut meal. Either preclinical or clinical studies indicate that PEA is potentially...

pubmed.ncbi.nlm.nih.gov

"Palmitoylethanolamide protects against the amyloid-β25-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease"

Palmitoylethanolamide Protects Against the Amyloid-β25-35-Induced Learning and Memory Impairment in Mice, an Experimental Model of Alzheimer Disease - PMC

Alzheimer disease (AD) is the most common form of neurodegenerative dementia. Amyloid-β deposition, neurofibrillary tangle formation, and neuro-inflammation are the major pathogenic mechanisms that in concert lead to memory dysfunction and decline ...

www.ncbi.nlm.nih.gov

Vascular dementia and aliamides: A new approach for the future

Vascular dementia and aliamides: A new approach for the future

OA Text is an independent open-access scientific publisher showcases innovative research and ideas aimed at improving health by linking research and practice to the benefit of society.

www.oatext.com

DHEA
Pregnenolone
“Pregnenolone sulfate and DHEA sulfate have also been found to improve cognition in animal studies[111][112][113][114][115][116][117][118]. In an animal model of b amyloid-induced amnesia, DHEA, DHEA sulfate, and pregnenolone sulfate attenuated amnesia in a dose-dependent manner[119]. Interestingly, inhibition of the steroid sulfatase enzyme improved the antiamnesic effect of DHEA sulfate[120][121], indicating that preventing neuroactive steroids from being converted out of their sulfate form may improve cognition.

“Nevertheless, the non-sulfated form of pregnenolone has been shown to improve cognition[122][123] and function[124][125] in schizophrenics. Schizophrenia is characterized by elevations in DHEA and DHEA sulfate and decreases in allopregnanolone, though it is yet unknown how pregnenolone is exerting its effect[126]. It was observed that changes in plasma steroid levels of pregnenolone and allopregnanolone correlated with functional improvements. Interestingly, studies indicate pregnenolone produces biphasic results, where lower dosed (30 mg/day) treatments produced better outcomes than higher dosed treatments (200 mg/day).”

The Power of Neuroactive Steroids

This article introduces the reader to the biosynthesis of neuroactive hormones and reviews what we know about their effects on cognition.

www.leoandlongevity.com

Great article about selegiline. Where does one procure selegiline?

 

[Cataceous]

Great article about selegiline. Where does one procure selegiline?

AllDayChemist is one place.

 

[Nelson Vergel]

I have been taking regular choline (350 mg) daily for a month and I can say my better focus is not a placebo effect.

 

[Nelson Vergel]

Unlocking the Potential of Choline Supplementation

Table of Contents Are you curious about the benefits of choline supplementation and how it can unlock your true potential? Choline is an essential nutrient that plays a crucial role in various bodily functions, from brain development to liver health. In this blog, we will provide you with a...

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