2 votes
Posted 13 October 2014 - 09:29 AM
where do you guys get the idea if you are undermethylated or overmethylated? i didnt know such tests even exist. thats like saying they already do tests on brain neurotransmitters too? sounds far fetched. just tell me it isnt one of those self test websites....
Posted 13 October 2014 - 10:28 AM
No self test website, mate. Here's my results: http://www.docdroid..../mthfr.pdf.html
I have addressed and fixed most of the +/+ ones there. My immune system has always been weak and the igG and igA tells us why.
Therefore I take a spirulina and chlorella smoothie (5ml of apple cider vinegar masks the awful taste) every morning with astragalus root powder, amongst other things in order to fix my igE, igG and igA antibodies. Just ordered some of Jarrow's Beta-1,3/1,6-D-Glucan. Seems promising.
Currently playing around with PEMT. Been struggling with CBS C699T, it has been hellish, but fixed it. Now I can focus on methylation.
You will see that I didn't win the genetic lottery if you check the pdf. There are many more SNPs, which I check with promethease (a program) when I have time.
where do you guys get the idea if you are undermethylated or overmethylated? i didnt know such tests even exist. thats like saying they already do tests on brain neurotransmitters too? sounds far fetched. just tell me it isnt one of those self test websites....
Posted 13 October 2014 - 12:38 PM
No self test website, mate. Here's my results: http://www.docdroid..../mthfr.pdf.html
I have addressed and fixed most of the +/+ ones there. My immune system has always been weak and the igG and igA tells us why.
Therefore I take a spirulina and chlorella smoothie (5ml of apple cider vinegar masks the awful taste) every morning with astragalus root powder, amongst other things in order to fix my igE, igG and igA antibodies. Just ordered some of Jarrow's Beta-1,3/1,6-D-Glucan. Seems promising.
Currently playing around with PEMT. Been struggling with CBS C699T, it has been hellish, but fixed it. Now I can focus on methylation.
You will see that I didn't win the genetic lottery if you check the pdf. There are many more SNPs, which I check with promethease (a program) when I have time.
where do you guys get the idea if you are undermethylated or overmethylated? i didnt know such tests even exist. thats like saying they already do tests on brain neurotransmitters too? sounds far fetched. just tell me it isnt one of those self test websites....
Are you undermethylated zenfood?
Posted 13 October 2014 - 01:45 PM
Hey man! I am not entirely sure. Leaning more towards to undermethylation. I have read about "under/over methylation" and I do not fit any of these categories perfectly. Basically everything except for the low homocysteine and high libido fits me. These are listed as common characteristics here: http://www.biobalanc...tal-illness.pdf
TMG really makes me feel good and is one of my top supplements now. Therefore it wouldn´t make any sense that I am lowering my already low homocysteine. In contrary, I believe that my homocysteine is skyrocket high. My eyesight is getting better (due to lower homocysteine I believe), I am experiencing visual and mood brightening effects from it.
No self test website, mate. Here's my results: http://www.docdroid..../mthfr.pdf.html
I have addressed and fixed most of the +/+ ones there. My immune system has always been weak and the igG and igA tells us why.
Therefore I take a spirulina and chlorella smoothie (5ml of apple cider vinegar masks the awful taste) every morning with astragalus root powder, amongst other things in order to fix my igE, igG and igA antibodies. Just ordered some of Jarrow's Beta-1,3/1,6-D-Glucan. Seems promising.
Currently playing around with PEMT. Been struggling with CBS C699T, it has been hellish, but fixed it. Now I can focus on methylation.
You will see that I didn't win the genetic lottery if you check the pdf. There are many more SNPs, which I check with promethease (a program) when I have time.
where do you guys get the idea if you are undermethylated or overmethylated? i didnt know such tests even exist. thats like saying they already do tests on brain neurotransmitters too? sounds far fetched. just tell me it isnt one of those self test websites....
Are you undermethylated zenfood?
Edited by Zenfood, 13 October 2014 - 01:46 PM.
Posted 13 October 2014 - 08:20 PM
No self test website, mate. Here's my results: http://www.docdroid..../mthfr.pdf.html
I have addressed and fixed most of the +/+ ones there. My immune system has always been weak and the igG and igA tells us why.
Therefore I take a spirulina and chlorella smoothie (5ml of apple cider vinegar masks the awful taste) every morning with astragalus root powder, amongst other things in order to fix my igE, igG and igA antibodies. Just ordered some of Jarrow's Beta-1,3/1,6-D-Glucan. Seems promising.
Currently playing around with PEMT. Been struggling with CBS C699T, it has been hellish, but fixed it. Now I can focus on methylation.
You will see that I didn't win the genetic lottery if you check the pdf. There are many more SNPs, which I check with promethease (a program) when I have time.
where do you guys get the idea if you are undermethylated or overmethylated? i didnt know such tests even exist. thats like saying they already do tests on brain neurotransmitters too? sounds far fetched. just tell me it isnt one of those self test websites....
i dont understand a thing about those "results" pdf you posted. not sure how you figure them out. was just curious if there are actual tests for methylation or not.
Posted 14 October 2014 - 02:35 PM
I decided to quit Noopept yesterday because it started to interfere with my working memory. My short term memory started to get worse.
My belief is that it is best used in short periods and not for chronic supplementation as I first believed. However, everyone is different.
Tried Bacopa today (165mg bacosides) and it has been really great on my mood and reduced anxiety better than anything I have ever tried in my life.
"Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress."
Thank you Bateau for sharing this information!
Seems that I have problems with dopamine D1/D2 receptors after all. Low dopamine D2 receptors or dopamine levels are associated with social anxiety, and anxiety in general, along with susceptibility to depression and low motivation.
Here is some info I have gathered how to improve short term memory:
These quotes are from the same study:
"Previous research has reported impaired performance on tasks of spatial working memory after administration of a D1-like antagonist."
"The intriguing results suggest a greater contribution of D2-like over D1-like receptors to both spatial working memory and object-location associative memory."
Source: http://www.ncbi.nlm....cles/PMC2099258
"The dopamine D1 but not D3 receptor plays a fundamental role in spatial working memory and BDNF expression in prefrontal cortex of mice." Source: http://www.ncbi.nlm....pubmed/22776159
My short term memory is horrible. The only things that have helped are ALCAR (acetylcholine), Huperzine A (acetylcholine) and methylphenidate (NET & DAT).
"Individual differences in visual-spatial attention and visual working memory are associated with acetylcholine- and dopamine-relevant genes. The efficiency of these 2 transmitter systems declines substantially during healthy aging. These declines, in part, contribute to age-related deficits in attention and working memory functions." Source: http://www.ncbi.nlm....pubmed/22103306
"These results suggested that supplementation with acetyl-L-carnitine improves spatial working memory deficits reduces oxidative stress and inhibits apoptotic cascade induced by hypoxia." Source: http://www.ncbi.nlm....pubmed/17610872
"Huperzine A (Acetylcholine) improves the mnemonic performance requiring working memory in monkeys." Source: http://www.ncbi.nlm..../pubmed/9918593
So improving spatial working memory deficits, increasing acetylcholine, improving D1/D2 receptor expression and upregulating D1/D2 receptors seems to be the ultimate working memory cure.
Edited by Zenfood, 14 October 2014 - 03:33 PM.
Posted 14 October 2014 - 03:48 PM
"The dopamine D1 but not D3 receptor plays a fundamental role in spatial working memory and BDNF expression in prefrontal cortex of mice."
I believe that my BDNF is very low. I have always been struggling with "thinking in pictures". When I read a story I do not create characters or surroundings in my mind. I store these as facts basically. This is why I wanted to try Noopept in the first place, because it increases BDNF. However, it seems that increasing D1 helps. Therefore I have concluded that my main problems are related to D1 and D2 receptors.
I would appreciate any feedback or ideas on how to specifically boost these receptors.
Thanks in advance.
Edited by Zenfood, 14 October 2014 - 03:50 PM.
Posted 14 October 2014 - 10:28 PM
this is late in the thread for a response on some of the supplements mentioned, but a few recommendations need warnings:
psoralea is genotoxic and causes DNA damage. otherwise you would have seen it everywhere in everything, i've bought it twice when researching this topic and abandoning it (and forgetting I ever researched it).
muira puama has strong MAOI properties and mixes badly with alot of things. i tried to use it in a supplement formulation and had to abandon it. i think the peruvians or brazilians who combine it with catuaba don't have the wide array of interacting chemicals in their diet the average westerner does, so mixing stims and MAOIs worked for them traditionally. (catuaba is great stuff though on its own, I recommend a tincture, if you dig into this topic it needs ethanolic extraction for all the goodies).
guanfacine potentially damages heart valves, clonidine appears to be a better option.
those things said, things that have worked for me very well have been phenylpiractem, which one blog I found stated the chemical structure of which looked almost exactly like ritalin crossed with piracetam. the effects seem to support this as well, also CDP-choline together (or alone) worked great in upregulating D2, since both substances facilitate this. Huperzine-A is one of the most underrated noots ever, it doesn't have the heart issues Galantamine does, it's plant based, cheap, and along with lion's mane mushroom (which you can find whole in chinese grocery store for a fraction of the price, like $4 for a bag of 6 or 7 tennis ball sized mushrooms, just eatem like a stale biscuit with a dark chocolate or coffee) are some of the best brain enhancement tools nature has to offer, and have helped my Inattentive ADD enormously.
Daily phenylpiracetam at 100mg for a year with coffee has started to cause mild chest discomfot however, but this may be because my tolerance has gone down due to upregulation so I need to greatly reduce dosage. I want to move away from direct stimulants for my issues so I will be trying Semax and Fasoracetam (with afobazol to replace phenibut for sleep) possibly with Clonidine for my issues.
Edited by Simon Silver, 14 October 2014 - 10:31 PM.
Posted 15 October 2014 - 03:51 AM
psoralea is a genus. which plant do you mean exactly? i checked one chemical present in some of those species called psoralen for a DNA damage, it seems to be related to inhibition of mitochondrial complex I, which is also inhibited by green tea, rasveratrol and metformin and all of them can be anti-carcinogen agents. if anything, its good for DNA damage of tumor cells?
i checked lots of positive reports and articles from wiki on guanfacine and not a single mention of heart valve damage. where do you get this from?
edit: i checked more on psoralen. its present in a lot of food we eat, mentioned few on wiki are figs, parsley and celery, do you think those foods actually cause DNA damage?
here is the damage report you probably talk about: Psoralen is a mutagen, and is used for this purpose in molecular biology research. Psoralen intercalates into the DNA and, on exposure to ultraviolet (UVA) radiation, can form covalent interstrand cross-links (ICL) with thymines preferentially at 5'-TpA sites in the genome, inducing apoptosis.
so its only DNA damaging when UV is combined with it on the skin.
Edited by normalizing, 15 October 2014 - 03:56 AM.
Posted 15 October 2014 - 12:19 PM
This study identified hepatic RCCs as targets for EGCG in swelling but not normal mitochondria, suggesting EGCG may trigger hepatotoxicity by worsening pre-existing mitochondria abnormalities.
http://www.ncbi.nlm....pubmed/24384371
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria.
In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS.
http://www.ncbi.nlm....pubmed/23291000
Moreover, Complex I is the primary source of ROS in a variety of pathological scenarios ranging from ageing to Parkinson's disease
http://jp.physoc.org.../552/2/335.full
Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species.
http://www.ncbi.nlm....pubmed/19059197
Inhibition of the complex is bad unless for cancer.
But some compounds may have a healthy effect as well
You never know.
Edited by Flex, 15 October 2014 - 12:28 PM.
Posted 15 October 2014 - 01:23 PM
Wow dude, thanks!
Have you tried pramiracetam? If so, what's the difference between them?
I have to agree that Huperzine A is underrated. It is awesome. I wish I could take it daily.
I have been thinking of growing my own Lion's mane at home for a while. I got all the equipment for that already.
Yeah, I'm currently stimulant free. Haven't touched methylphenidate for a month. Tried Modafinil recently, but it gives me brain fog and impaired speech. So not going to touch that stuff again.
this is late in the thread for a response on some of the supplements mentioned, but a few recommendations need warnings:
psoralea is genotoxic and causes DNA damage. otherwise you would have seen it everywhere in everything, i've bought it twice when researching this topic and abandoning it (and forgetting I ever researched it).
muira puama has strong MAOI properties and mixes badly with alot of things. i tried to use it in a supplement formulation and had to abandon it. i think the peruvians or brazilians who combine it with catuaba don't have the wide array of interacting chemicals in their diet the average westerner does, so mixing stims and MAOIs worked for them traditionally. (catuaba is great stuff though on its own, I recommend a tincture, if you dig into this topic it needs ethanolic extraction for all the goodies).
guanfacine potentially damages heart valves, clonidine appears to be a better option.
those things said, things that have worked for me very well have been phenylpiractem, which one blog I found stated the chemical structure of which looked almost exactly like ritalin crossed with piracetam. the effects seem to support this as well, also CDP-choline together (or alone) worked great in upregulating D2, since both substances facilitate this. Huperzine-A is one of the most underrated noots ever, it doesn't have the heart issues Galantamine does, it's plant based, cheap, and along with lion's mane mushroom (which you can find whole in chinese grocery store for a fraction of the price, like $4 for a bag of 6 or 7 tennis ball sized mushrooms, just eatem like a stale biscuit with a dark chocolate or coffee) are some of the best brain enhancement tools nature has to offer, and have helped my Inattentive ADD enormously.
Daily phenylpiracetam at 100mg for a year with coffee has started to cause mild chest discomfot however, but this may be because my tolerance has gone down due to upregulation so I need to greatly reduce dosage. I want to move away from direct stimulants for my issues so I will be trying Semax and Fasoracetam (with afobazol to replace phenibut for sleep) possibly with Clonidine for my issues.
Posted 15 October 2014 - 01:32 PM
Flex, this is some valuable information for me. Maybe this is a coincidence, but did you check my SNPs? My NDUFS3 and NDUFS 7 are damaged, which means that my Complex I pathway doesn't work the way it should.
I do have mitochondrial dysfunction. My SOD A16V gene is half functioning as well. I'm discontinuing EGCG. Going to experiment with stronger Gynostemma extract (70:1 ratio, equals 28g of the plant) and see if it helps me. Never noticed anything from CoQ10 (300mg Ubiquinol)+Shilajit (300mg)+PQQ(20mg)+Sulblingual NADH (20mg) and several other mitochondrial enhancers. I am very sedentary and I believe it is due to lower ATP. This is why I've done powerlifting, but the downside is that it is too taxing on the central nervous system once you get up to an advanced level. Makes me kind of want to start injecting myself with testosterone enanthate so that I could be able to continue powerlifting. It heals the central nervous system and should also upregulate D2 receptors at the same time.
Any ideas on how to aid my Complex I? CoQ10&co doesn't really help. Spirulina and Gynostemma increases SOD activity, so I am relying on them for now.
The best thing so far was 2x1500mg niacinamide extended release tablets. They gave me energy and a sense of calmness.
This study identified hepatic RCCs as targets for EGCG in swelling but not normal mitochondria, suggesting EGCG may trigger hepatotoxicity by worsening pre-existing mitochondria abnormalities.
http://www.ncbi.nlm....pubmed/24384371
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria.
In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS.
http://www.ncbi.nlm....pubmed/23291000
Moreover, Complex I is the primary source of ROS in a variety of pathological scenarios ranging from ageing to Parkinson's disease
http://jp.physoc.org.../552/2/335.full
Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species.
http://www.ncbi.nlm....pubmed/19059197
Inhibition of the complex is bad unless for cancer.
But some compounds may have a healthy effect as well
You never know.
Edited by Zenfood, 15 October 2014 - 01:33 PM.
Posted 15 October 2014 - 03:02 PM
"As with all mitochondrial diseases, there is no cure for Complex I deficiency. A variety of treatments, which may or may not be effective, can include such metabolic therapies as: riboflavin, thiamine, biotin, co-enzyme Q10, carnitine, and the ketogenic diet." Source: http://www.umdf.org/..._DEFICIENCY.pdf
Going to experiment with Carnitine Fumarate. Going to try out the ketogenic diet again. This time without MCT and Coconut oil, which upregulates Th2 and worsens allergies (elevated histamine).
"Dietary MCT promote allergic sensitization and anaphylaxis by affecting antigen absorption and availability and by stimulating Th2 responses."
Source: http://www.ncbi.nlm....les/PMC3563838/
Posted 15 October 2014 - 05:19 PM
Flex, this is some valuable information for me. Maybe this is a coincidence, but did you check my SNPs? My NDUFS3 and NDUFS 7 are damaged, which means that my Complex I pathway doesn't work the way it should.
I do have mitochondrial dysfunction. My SOD A16V gene is half functioning as well. I'm discontinuing EGCG. Going to experiment with stronger Gynostemma extract (70:1 ratio, equals 28g of the plant) and see if it helps me. Never noticed anything from CoQ10 (300mg Ubiquinol)+Shilajit (300mg)+PQQ(20mg)+Sulblingual NADH (20mg) and several other mitochondrial enhancers. I am very sedentary and I believe it is due to lower ATP. This is why I've done powerlifting, but the downside is that it is too taxing on the central nervous system once you get up to an advanced level. Makes me kind of want to start injecting myself with testosterone enanthate so that I could be able to continue powerlifting. It heals the central nervous system and should also upregulate D2 receptors at the same time.
Any ideas on how to aid my Complex I? CoQ10&co doesn't really help. Spirulina and Gynostemma increases SOD activity, so I am relying on them for now.
The best thing so far was 2x1500mg niacinamide extended release tablets. They gave me energy and a sense of calmness.
This study identified hepatic RCCs as targets for EGCG in swelling but not normal mitochondria, suggesting EGCG may trigger hepatotoxicity by worsening pre-existing mitochondria abnormalities.
http://www.ncbi.nlm....pubmed/24384371
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria.
In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS.
http://www.ncbi.nlm....pubmed/23291000
Moreover, Complex I is the primary source of ROS in a variety of pathological scenarios ranging from ageing to Parkinson's disease
http://jp.physoc.org.../552/2/335.full
Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species.
http://www.ncbi.nlm....pubmed/19059197
Inhibition of the complex is bad unless for cancer.
But some compounds may have a healthy effect as well
You never know.
Specifically it's testosterone being in a proper ratio with estradiol, but ultimately it is brain free t which converts to estrogen which sustains and increases d2 expression....however, too much or over the border estrogen will do the opposite, so basically low-normal range of estrogen is good for increasing dopamine expression.
Edited by Area-1255, 15 October 2014 - 05:19 PM.
Posted 15 October 2014 - 09:43 PM
Have you tried pramiracetam? If so, what's the difference between them?
You can notice the amphetamine-like structure in the body/mental feel, pram to me just felt like a much more forceful piracetam or oxiracetam and lacked the sharpness and stimulation. I'm kind of habituated to it, not addicted per se but I really dislike the step down in mental effects when I go without it. Hopefully Semax will be a good replacement, but I will probably take Phenylpiracetam every day till then. When I was sick recently and wanted to go without stims Huperzine filled the gap well, it is sharp and almost stimulating.
Edited by Simon Silver, 15 October 2014 - 09:43 PM.
Posted 15 October 2014 - 10:50 PM
Thanks!
This study hasn't been cited on here longecity yet. It is quite new.
http://www.ncbi.nlm....pubmed/24086396
Could this mean that it is safe to use it more regularly?
Have you tried pramiracetam? If so, what's the difference between them?
You can notice the amphetamine-like structure in the body/mental feel, pram to me just felt like a much more forceful piracetam or oxiracetam and lacked the sharpness and stimulation. I'm kind of habituated to it, not addicted per se but I really dislike the step down in mental effects when I go without it. Hopefully Semax will be a good replacement, but I will probably take Phenylpiracetam every day till then. When I was sick recently and wanted to go without stims Huperzine filled the gap well, it is sharp and almost stimulating.
Posted 15 October 2014 - 10:52 PM
Great stuff man. Do you think sublingual pregnenolone could help in any way? I know it's a neurosteroid. I've tried 100mg sublingually today without noticing anything (reputable brand, high quality). No heart palpitations or rise on cortisol. Maybe I should up the dose and see what it does?
Flex, this is some valuable information for me. Maybe this is a coincidence, but did you check my SNPs? My NDUFS3 and NDUFS 7 are damaged, which means that my Complex I pathway doesn't work the way it should.
I do have mitochondrial dysfunction. My SOD A16V gene is half functioning as well. I'm discontinuing EGCG. Going to experiment with stronger Gynostemma extract (70:1 ratio, equals 28g of the plant) and see if it helps me. Never noticed anything from CoQ10 (300mg Ubiquinol)+Shilajit (300mg)+PQQ(20mg)+Sulblingual NADH (20mg) and several other mitochondrial enhancers. I am very sedentary and I believe it is due to lower ATP. This is why I've done powerlifting, but the downside is that it is too taxing on the central nervous system once you get up to an advanced level. Makes me kind of want to start injecting myself with testosterone enanthate so that I could be able to continue powerlifting. It heals the central nervous system and should also upregulate D2 receptors at the same time.
Any ideas on how to aid my Complex I? CoQ10&co doesn't really help. Spirulina and Gynostemma increases SOD activity, so I am relying on them for now.
The best thing so far was 2x1500mg niacinamide extended release tablets. They gave me energy and a sense of calmness.
This study identified hepatic RCCs as targets for EGCG in swelling but not normal mitochondria, suggesting EGCG may trigger hepatotoxicity by worsening pre-existing mitochondria abnormalities.
http://www.ncbi.nlm....pubmed/24384371
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria.
In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS.
http://www.ncbi.nlm....pubmed/23291000
Moreover, Complex I is the primary source of ROS in a variety of pathological scenarios ranging from ageing to Parkinson's disease
http://jp.physoc.org.../552/2/335.full
Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species.
http://www.ncbi.nlm....pubmed/19059197
Inhibition of the complex is bad unless for cancer.
But some compounds may have a healthy effect as well
You never know.
Specifically it's testosterone being in a proper ratio with estradiol, but ultimately it is brain free t which converts to estrogen which sustains and increases d2 expression....however, too much or over the border estrogen will do the opposite, so basically low-normal range of estrogen is good for increasing dopamine expression.
Posted 16 October 2014 - 12:45 AM
Great stuff man. Do you think sublingual pregnenolone could help in any way? I know it's a neurosteroid. I've tried 100mg sublingually today without noticing anything (reputable brand, high quality). No heart palpitations or rise on cortisol. Maybe I should up the dose and see what it does?
Flex, this is some valuable information for me. Maybe this is a coincidence, but did you check my SNPs? My NDUFS3 and NDUFS 7 are damaged, which means that my Complex I pathway doesn't work the way it should.
I do have mitochondrial dysfunction. My SOD A16V gene is half functioning as well. I'm discontinuing EGCG. Going to experiment with stronger Gynostemma extract (70:1 ratio, equals 28g of the plant) and see if it helps me. Never noticed anything from CoQ10 (300mg Ubiquinol)+Shilajit (300mg)+PQQ(20mg)+Sulblingual NADH (20mg) and several other mitochondrial enhancers. I am very sedentary and I believe it is due to lower ATP. This is why I've done powerlifting, but the downside is that it is too taxing on the central nervous system once you get up to an advanced level. Makes me kind of want to start injecting myself with testosterone enanthate so that I could be able to continue powerlifting. It heals the central nervous system and should also upregulate D2 receptors at the same time.
Any ideas on how to aid my Complex I? CoQ10&co doesn't really help. Spirulina and Gynostemma increases SOD activity, so I am relying on them for now.
The best thing so far was 2x1500mg niacinamide extended release tablets. They gave me energy and a sense of calmness.
This study identified hepatic RCCs as targets for EGCG in swelling but not normal mitochondria, suggesting EGCG may trigger hepatotoxicity by worsening pre-existing mitochondria abnormalities.
http://www.ncbi.nlm....pubmed/24384371
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria.
In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS.
http://www.ncbi.nlm....pubmed/23291000
Moreover, Complex I is the primary source of ROS in a variety of pathological scenarios ranging from ageing to Parkinson's disease
http://jp.physoc.org.../552/2/335.full
Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species.
http://www.ncbi.nlm....pubmed/19059197
Inhibition of the complex is bad unless for cancer.
But some compounds may have a healthy effect as well
You never know.
Specifically it's testosterone being in a proper ratio with estradiol, but ultimately it is brain free t which converts to estrogen which sustains and increases d2 expression....however, too much or over the border estrogen will do the opposite, so basically low-normal range of estrogen is good for increasing dopamine expression.
Maybe pregnenolone plus DHEA...one particular product I got a nice drop in cortisol from, and felt overall better on - almost euphoric was ergogenix ergobolic...it's a cortisol blocker with black tea theflavins, sutherlandia and momordica which is a 3b hsd inhibitor, thus inhibiting cortisol synthesis right by the enzymes itself while facilitating a cascade of anabolic processes and more androgenic metabolites being produced.
Posted 18 October 2014 - 01:44 PM
Methylphenidate. Why it is good and not neurotoxic in lower doses.
There has been a lot of talk that methylphenidate might be neurotoxic. But I have looked at this and did not find strong evidence for this.
Methylphenidate Exposure Induces Dopamine Neuron Loss and Activation of Microglia in the Basal Ganglia of Mice
mouse mg/kg divided with 12,30769230769231
the result above * your own weight in kg
= answer
"no change in SNpc DA neuron number"
0,999/12,30769230769231 = 0,08116875
0,08116875 * 70 (my weight in kg) ~ 5,7mg
" 20% reduction of SNpc DA neurons"
10 / 12,30769230769231 = 0,8124999999999998
0,8124999999999998 * 70 ~ 57mg
Please note that 57mg is 10x more than the recommended dose. Also, it seems that 57mg was instant release and not an extended release.
How about spreading the doses, let's say 5-10mg every 4 hour like normal people do? or just take a Concerta.
The article mensions that Excessive dopamine can induce oxidative stress and inflammation. Well, of course 57mg of methylphenidate creates excessive levels of dopamine. This is megadosing! People usually get pleasing effects from just 5-10mg every 4th hour.
Overall it seems that methylphenidate is great. Look at these studies:
Changes in plasma Brain-derived neurotrophic factor (BDNF) levels induced by methylphenidate in children with Attention deficit-hyperactivity disorder (ADHD).
"Our findings demonstrated both short- and long-term effects of Ritalin on frontal serotonergic system after withdrawal period." Source: http://www.ncbi.nlm....pubmed/23748891
"The study also established that Ritalin® strengthens synapses and enhances neuroplasticity."
Sources: http://drugdiscovery...rcuits-revealed , http://www.nature.co...bs/nn.2506.html
Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review
"In this study, the author reported that a single dose of MPH significantly increased subjective rating of a mathematical task as being interesting, exciting, motivating and less tiresome, while such an effect was not found in ratings of a passive task (looking at pictures)." Source: http://www.gwern.net...10-repantis.pdf
Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review
"Methylphenidate and modafinil both enhanced perceptual processing speed in participants with low baseline (placebo) performance. These improvements correlated with subjective alertness. Furthermore, we observed differential plasma level-dependent effects of methylphenidate in lower and higher performing participants: higher plasma levels led to a greater improvement in low-performing participants and to decreasing improvement in high-performing participants. Modafinil enhanced visual short-term memory storage capacity in low-performing participants." Source: http://www.ncbi.nlm....pubmed/20352415
Three-month treatment course of methylphenidate increases plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in attention deficit hyperactivity disorder. "There was a significant increase in serum levels of DHEA and DHEA-S but not in circulatory levels of cortisol" Source: http://www.ncbi.nlm....pubmed/14586159
Posted 29 November 2014 - 09:29 PM
Hey!
I do powerlifting. Have been doing this for the past three years, but it hasn't helped. Not sure what you mean with getting to a high testosterone state. The only possible way to do this is to start juicing.I already eat lots of fats (cholesterol -> pregnenolone -> all kinds of hormones)
How about:
"Three-month treatment course of methylphenidate increases plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in attention deficit hyperactivity disorder."http://www.ncbi.nlm....pubmed/14586159
Ritalin! Looks promising.
Chronic caffeine treatment is not for me, trust me. I have elevated Th2 levels and caffeine makes it worse.
http://selfhacked.co...-th2-dominance/
DAA could work (but has to be used chronically then and it could be dangerous/neurotoxic?). I have a bag of 500g DAA at home laying. Do you think I should start using it again? I have used it in the past. I have also experimented with NMDA, took 30mg before sleep for a whole month. Needless to say, it didn't make things better.
Hmmm. doesn't going to the Gym or intensive workout or Cardio up-regulate dopamine receptors long term ? but as you say you have been doing power-lifting for 3 years and it hasn't helped -
The only reason I can think of as to why it didn't do anything is because you used a powerful stimulant methylphenidate between that same period while you were lifting starting from a high dosage and then gradually shifting to a low dosage .
and methylphenidate are known to down-regulate the Dopamine receptors and cause other problems in the dopamine region
So I guess the stimulant overpowered the workout benefit and net effect didn't change if not worse = dopamine downregulation
Someone correct me if I'm wrong !
Edited by forexworld12, 29 November 2014 - 09:30 PM.
Posted 29 November 2014 - 09:36 PM
Hey!
I do powerlifting. Have been doing this for the past three years, but it hasn't helped. Not sure what you mean with getting to a high testosterone state. The only possible way to do this is to start juicing.I already eat lots of fats (cholesterol -> pregnenolone -> all kinds of hormones)
How about:
"Three-month treatment course of methylphenidate increases plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in attention deficit hyperactivity disorder."http://www.ncbi.nlm....pubmed/14586159
Ritalin! Looks promising.
Chronic caffeine treatment is not for me, trust me. I have elevated Th2 levels and caffeine makes it worse.
http://selfhacked.co...-th2-dominance/
DAA could work (but has to be used chronically then and it could be dangerous/neurotoxic?). I have a bag of 500g DAA at home laying. Do you think I should start using it again? I have used it in the past. I have also experimented with NMDA, took 30mg before sleep for a whole month. Needless to say, it didn't make things better.
Hmmm. doesn't going to the Gym or intensive workout or Cardio up-regulate dopamine receptors long term ? but as you say you have been doing power-lifting for 3 years and it hasn't helped -
The only reason I can think of as to why it didn't do anything is because you used a powerful stimulant methylphenidate between that same period while you were lifting starting from a high dosage and then gradually shifting to a low dosage .
and methylphenidate are known to down-regulate the Dopamine receptors and cause other problems in the dopamine region
So I guess the stimulant overpowered the workout benefit and net effect didn't change if not worse = dopamine downregulation
Someone correct me if I'm wrong !
You are correct forexworld, also note, that walking for long periods of time , and resistance training stimulates histamine production by means of histidine decarboxylase stimulation; which allows the body/brain to synthesize more histamine from the amino acid histidine, and thus , accounts for post exercise and intra-exercise (especially cardio) vasodilation.
http://jp.physoc.org...509/2/587.short
http://ep.physoc.org...nt/98/1/7.short
Posted 09 December 2014 - 07:22 AM
Zenfood,
Be careful with bacopa. Search pubmed for studies on how bacopa effects Leydig cells in the testicles. I used it for months for cognitive rehab after an injury of sorts and ended up with low testosterone and shrunken testicles. These things did not go away.
Posted 11 December 2014 - 07:53 AM
oh my. first time i see bacopa associated with such nasty negative effect. people on this forum have been recomending and careless promoting it as all natural safe and effective herb for ages now. good to hear other sides to this FINALLY.
Posted 11 December 2014 - 02:49 PM
Edited by Metagene, 11 December 2014 - 03:09 PM.
Posted 11 December 2014 - 06:36 PM
This isn't the first time normalizing. Don't be so dramatic. See post #8 & #25 http://www.longecity...-a-med-student/
Evaluation of antifertility potential of Brahmi in male mouse.
BACKGROUND: The purpose of the present study was to evaluate the effect of Bacopa monnieri (Brahmi) on fertility of male laboratory mouse.
STUDY DESIGN: Mice of the Parkes (P) strain were orally administered Brahmi (250 mg/kg body weight/day, for 28 and 56 days), and effect of the treatment on reproductive organs and fertility was investigated. Recovery and toxicological studies were also carried out.
RESULTS: The treatment caused reduction in motility, viability, morphology, and number of spermatozoa in cauda epididymidis. Histologically, testes in mice treated with the plant extract showed alterations in the seminiferous tubules, and the alterations included intraepithelial vacuolation, loosening of germinal epithelium, exfoliation of germ cells and occurrence of giant cells. In severe cases, the tubules were lined by only Sertoli cells or Sertoli cells, spermatogonia and spermatocytes. Significant reductions were also noted in height of the germinal epithelium and diameter of the seminiferous tubules in Brahmi-treated mice compared to controls. Epididymis in treated males showed slight alterations in histological appearance. The treatment had no effect on levels of testosterone, alanine aminotransferase, aspartate aminotransferase and creatinine in blood serum, hematological parameters and on liver and kidney histoarchitecture. In Brahmi-treated males, libido remained unaffected, but fertility was notably suppressed. The alterations caused in the above reproductive endpoints by the plant extract were reversible, and by 56 days of treatment withdrawal, the parameters recovered to control levels.
CONCLUSIONS: The results in P mice thus suggest that Brahmi treatment causes reversible suppression of spermatogenesis and fertility, without producing apparent toxic effects.
http://www.ncbi.nlm....ubmed/19041444/
I saw this as well, years back, if I took a high dose of bacopa, on week two, I would be getting testicle pain and soft glans. Not good ..good for focus, but only at low doses.
Posted 15 February 2015 - 03:47 PM
Zenfood hi,
How it's going? You didn't post for long here.
Hey man! Thanks for asking 
I've been feeling a lot better lately. I stopped powerlifting and switched over to body building. I feel much better from this. I think I suffered from CNS fatigue before. Now I don't kill myself, I stop when my "brain" says it's enough. No more "No pain, no gain-mentality". I also noticed that training legs less frequently makes me more energetic and I just recover much faster.
Also, I took 210mg/day of OptiZinc for 30 days. It made my pee flow WAY better (basically had really bad flow and I thought it was normal), enhanced my libido, removed muscle knots and improved my joints, more lucid dreams, now I visualize much better and think in pictures!, etc. so I from my own experience hard training depletes the body from zinc, magnesium and potassium. Excess calcium interferes with magnesium and zinc absorption (this is why I quit dairy a couple of months ago).
Hard training and a caloric deficit is very taxing to the central nervous system. However, I still have problems with dopamine, but I have found a nice combination for it. My libido is much better now when I'm on a caloric suffiency/surplus diet and after the zinc. I took 25g of gelatinized Maca powder for 10 days and I feel that it balanced my hormones or something much faster.
Now, I've been trying Modafinil, strattera, concerta, huperzine a and different combinations.
Thanks to Stinkorninjor I realized that caffeine makes my symptoms worse so I will never touch it again. It raises cAMP levels in the brain and those with ADD already have too high levels to begin with...
The best combination I've found so far is concerta (36mg) + slow release niacinamide (1500mg).
This combination doesn't give me the jitters, the usual anxiety, the frequent urination, the insane thirst, the dysphoria/crash I usually experience afterwards, etc. I just feel very normal and I have tons of energy. I just make sure to supplement with magnesium and potassium (or eat lots of spinach), because as I understand it can deplete these.
It's also important to have something in the stomach all the time in order to avoid hepatotoxicity from slow release niacinamide. Taking it on an empty stomach is no joke and could result to irreversible liver damages.
When I feel that I start experiencing tolerance I go over to modafinil or huperzine a for a while.
200mg Huperzine A, (max 3 times a week) is amazing stuff. I'm sure it affects dopamine and noradrenalin somehow, it can't just be an AchE inhibitor only.
This affects my organizational skills, motivation, cognitive skills, etc. slightly better than modafinil.
I'm going to try out concerta + intuniv soon when I got my hands on the latter. Seems like awesome stuff. However I am very satisfied with the concerta and niacinamide treatment. I must say that it I'm much more happier, calmer, focused, future oriented and optimistic with it than without it.
I have just accepted that in order to function optimally in this society I just have to cycle between modafinil, huperzine a and concerta+niacinamide.
I mean, I've tried everything for the past two years. No dairy, no gluten, only real whole foods, veggies, best quality vitamins and minerals, >1000mg DHA each day, sufficient healthy fats, megadosing magnesium, etc. I'm continuing with this regimen even if it hasn't affected my motivation and focus one bit. However my brain isn't as clouded as it used to be and I don't experience brain fog anymore, I have less acne, better skin, better nails, etc. so therefore I'm going to eat clean until I die.
The best thing is that I don't ruminate anymore. I don't care if there are some flaws here and there in this text. Why should I waste lots of time in fixing details when everybody ultimately understands what I'm trying to say.
My "Zenhedonia stack":
- Life extension, One per day multivitamin
- Omega 3, 10ml (>1000mg DHA)
- Magnesium malate/chelate (>600mg magnesium)
- Megadosing with zinc picolinate/L-Optizinc for a short while
- Lots of gelatinized maca for a short while
- Caloric sufficiency/surplus
- Avoiding coffee
- Medium to high fat diet
- Concerta + slow release niacinamide (cycle with modafinil and huperzine a)
- Sunlamp (Very important for me, I live in Finland, haven't experienced SAD this year!)
Nicotinamide attenuates methamphetamine-induced striatal dopamine depletion in rats.
http://grande.nal.us...s&therow=551994
D-amphetamine-induced depletion of energy and dopamine in the rat striatum is attenuated by nicotinamide pretreatment.
http://www.ncbi.nlm....pubmed/10566977
Edited by Zenfood, 15 February 2015 - 03:51 PM.
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