4 votes
Posted 03 September 2014 - 06:15 PM
You should have seen some benefit from methylB12 but you said you felt better on hydrxyB12. Any ideas why ?
I'm homozygote for MTRR A664A rs1802059 AG +/+ and hetero for a few others and I wonder if I should include hydroxy of dibencozide in addition to methyl. Thanks.
Posted 05 September 2014 - 09:23 PM
You should have seen some benefit from methylB12 but you said you felt better on hydrxyB12. Any ideas why ?
I'm homozygote for MTRR A664A rs1802059 AG +/+ and hetero for a few others and I wonder if I should include hydroxy of dibencozide in addition to methyl. Thanks.
It seems like methylation isn't a big problem for me, but low BH4 synthesis is. Methyl B12 can reduce BH4 synthesis futher, which is the opposite of what I want. Hydroxocobalamin doesn't affect it at all. The reason I take B12 at all is that I want to avoid "methyl trapping", which is when methyl folate uses up all the B12 in the cells. The low intracellular B12 will then cause the cells to expel folate.
Edited by Chadwick, 05 September 2014 - 09:33 PM.
Posted 25 September 2014 - 01:29 PM
Dealing with exact issue as OP, but with the addition of social anxiety and delusional thinking. Tried A-Z, B complex, B6, P5P, zinc, Mfolate, MB12 etc. etc. etc. without any effect. I'm not a drinker. If the NMDA upregulation by alcohol theory is true, then it could explain why the people I grew up with (weekend alcoholics) are so far ahead of life than me (in terms of success).
There are rare occasions when I achieve a dopa high with the same diet I'm on for months now. It might be a sleep quality issue. With the high I'm much more talkative; infact, overly talkative. Anxiety lessens and my thinking becomes sharp and instant. It also makes me want to be spiritual.
Going to try Phenibut and report back. It's supposed to have the exact effects of alcohol without the nasty crap. Should lower acetylcholine and boost dopamine in theory...
Edited by Steve-22, 25 September 2014 - 01:35 PM.
Posted 26 September 2014 - 09:34 AM
Dealing with exact issue as OP, but with the addition of social anxiety and delusional thinking. Tried A-Z, B complex, B6, P5P, zinc, Mfolate, MB12 etc. etc. etc. without any effect. I'm not a drinker. If the NMDA upregulation by alcohol theory is true, then it could explain why the people I grew up with (weekend alcoholics) are so far ahead of life than me (in terms of success).
There are rare occasions when I achieve a dopa high with the same diet I'm on for months now. It might be a sleep quality issue. With the high I'm much more talkative; infact, overly talkative. Anxiety lessens and my thinking becomes sharp and instant. It also makes me want to be spiritual.
Going to try Phenibut and report back. It's supposed to have the exact effects of alcohol without the nasty crap. Should lower acetylcholine and boost dopamine in theory...
Normally, warning people about the possible consequences of taking too much phenibut is a dead beat horse around here, but since you seem to be new, at least to longecity -
Be extremely carefull with this substance. I'd strongly advise to do a lot of research here and read a few of the horrifying withdrawl stories about it, before actually trying it.
It is a great anxiolytic if used very sporadically/occasionally ( maybe once a week) - I do just that myself. However, people who overdose and use it for too long consecutively get horrible withdrawlsymptoms that can last for months because of agressive, chronic downregulation of GABA receptors.
It is in no way a long term solution for your symptoms.
Now, if you actually meant taking it instead of alcohol only on the weekends, that MIGHT be manageable. Just don't overdo it, I've seen enough Phenibut casualties... 
Posted 26 September 2014 - 01:02 PM
Dealing with exact issue as OP, but with the addition of social anxiety and delusional thinking. Tried A-Z, B complex, B6, P5P, zinc, Mfolate, MB12 etc. etc. etc. without any effect. I'm not a drinker. If the NMDA upregulation by alcohol theory is true, then it could explain why the people I grew up with (weekend alcoholics) are so far ahead of life than me (in terms of success).
There are rare occasions when I achieve a dopa high with the same diet I'm on for months now. It might be a sleep quality issue. With the high I'm much more talkative; infact, overly talkative. Anxiety lessens and my thinking becomes sharp and instant. It also makes me want to be spiritual.
Going to try Phenibut and report back. It's supposed to have the exact effects of alcohol without the nasty crap. Should lower acetylcholine and boost dopamine in theory...
Normally, warning people about the possible consequences of taking too much phenibut is a dead beat horse around here, but since you seem to be new, at least to longecity -
Be extremely carefull with this substance. I'd strongly advise to do a lot of research here and read a few of the horrifying withdrawl stories about it, before actually trying it.
It is a great anxiolytic if used very sporadically/occasionally ( maybe once a week) - I do just that myself. However, people who overdose and use it for too long consecutively get horrible withdrawlsymptoms that can last for months because of agressive, chronic downregulation of GABA receptors.
It is in no way a long term solution for your symptoms.
Now, if you actually meant taking it instead of alcohol only on the weekends, that MIGHT be manageable. Just don't overdo it, I've seen enough Phenibut casualties...
Thanks man! 
Posted 13 April 2015 - 07:58 PM
So much love for the OP, and everybody else who's contributed to this thread - it's fantastic! I have very similar experiences to many posted here, but symptoms centred round fatigue, and a constant mope.
I just wondered if anybody had any updates or new findings, as the post's been inactive for a while. It's really interesting to find out what has helped other people in similar situations.
I am 2 days into 5x 800mcg solgar metafolin but yet to experience any change, and mucuna appeared to be ineffective too. I wondered if absolutely no change on these suggests it might not be dopamine related for myself? I think the 23andme test is a good way forward though unaffordable at the moment. 
Thanks again everyone, please please keep adding to this!
Posted 17 April 2015 - 09:37 AM
Chronic alcohol use has had similar effects on me. Ironically I tend to hate drinking alcohol and generally do not drink. It makes me feel drowsy and generally lousy but if I keep drinking then in a matter of days I become more accustomed to it and my mind flows more freely and I feel more like my old self. I feel like there is so much more life in me. Less depression, less anhedonia, more desire to be around people etc.
This may be due to alcohol's ability to raise cortisol levels. My cortisol is very low so it makes a lot of sense. I rather not go back to alcohol but it frustrates me that it's difficult for me to feel well unless I do take up drinking. How unfortunate. Surely there must be other ways but it's been difficult for me to figure out. Gabapentin has some remarkable effects on mood but builds tolerance quite quickly.
Edited by AlexCanada, 17 April 2015 - 09:37 AM.
Posted 16 June 2015 - 05:06 PM
Very interesting thread. Any updates on your progress, Chadwick? Is your regimen still effective?
I relate to many of the symptoms that you described in your original posts and have experimented with methyl donors. I am homozygous for the MTHFR C667T mutation, so by all rights I should benefit greatly from methyl folate and related supplements. In the beginning I had some success, but now methyl folate, methyl b12, and SAM-E all put me into an absolute brainless stupor following a brief rush of energy. Each one will do this to me on its own even in the absence of the others.
It's funny--all the overmethylation symptoms you read about online relate to overstimulation. You rarely hear about methyl donors causing brain-dead zombie syndrome. I'd kill for some overstimulation!
Anyway, due to my genetics it seems that methyl donors really should have a place in my regimen if I can just figure out how to benefit from them. You seem to have found a good balance. How's it going for you?
Anyone else having success with methyl donors? Has anyone else experienced insane brain fog on them?
Posted 16 June 2015 - 05:33 PM
Very interesting thread. Any updates on your progress, Chadwick? Is your regimen still effective?
I relate to many of the symptoms that you described in your original posts and have experimented with methyl donors. I am homozygous for the MTHFR C667T mutation, so by all rights I should benefit greatly from methyl folate and related supplements. In the beginning I had some success, but now methyl folate, methyl b12, and SAM-E all put me into an absolute brainless stupor following a brief rush of energy. Each one will do this to me on its own even in the absence of the others.
It's funny--all the overmethylation symptoms you read about online relate to overstimulation. You rarely hear about methyl donors causing brain-dead zombie syndrome. I'd kill for some overstimulation!
Anyway, due to my genetics it seems that methyl donors really should have a place in my regimen if I can just figure out how to benefit from them. You seem to have found a good balance. How's it going for you?
Anyone else having success with methyl donors? Has anyone else experienced insane brain fog on them?
My regimen is still going strong, as effective as it was a year ago 
I too get brain fog from most methyl donors (methyl-B12, TMG, SAMe), plus fatigue and a total lack of interest in social interactions. This I believe has to do with that I am homozygous for the val158met variation of the COMT (Catechol-O-methyl transferase) gene. This variation makes the COMT enzyme more active, and as it uses methyl groups for breaking down dopamine, norepinephrine and epinephrine, an excess of free methyl groups results in too low levels of these neurotransmitters. People with the val158met variation of COMT have a tendency towards getting fatigued/brain fogged from methyl donors, while people without the val158met variation get stimulated.
This is why I use hydroxy-B12 instead of methyl-B12 - the combination of methylfolate and hydroxy-B12 increases my BH4 and dopamine without changing my methylation very much. This works great for me. The only side effect I have is that my hemoglobin is somewhat high from constantly having high plasma levels of folate and B12, but it's not giving me any real symptoms.
Posted 16 June 2015 - 07:42 PM
My regimen is still going strong, as effective as it was a year ago
This is why I use hydroxy-B12 instead of methyl-B12 - the combination of methylfolate and hydroxy-B12 increases my BH4 and dopamine without changing my methylation very much. This works great for me. The only side effect I have is that my hemoglobin is somewhat high from constantly having high plasma levels of folate and B12, but it's not giving me any real symptoms.
Thanks for the quick reply! I am actually met/met for the val158met variation (against all odds), and I still get crazy fatigue and brain fog from methyl donors, though maybe it takes longer for this overload to occur since my COMT enzyme is less active.
I've been resetting methylation with niacin/niacinamide the past few days (assuming that's not a myth) and will try adding a low dose of methyl folate back in, along with some non-methyl b12. Any problem with cyanocobalamin in your opinion?
Recently I decided to give iron supplements a shot on the off chance I was deficient. I haven't been tested for iron levels and know it's not advisable to mess around with unnecessarily, but I was a bit desperate and figured I'd only continue if I noticed a benefit. Oh man, what a difference in terms of cognition and energy. I believe you said in an earlier post that you noticed a similar benefit from iron.
Anyway, between the iron and cutting way back on my methyl donors, I believe I am seeing a light at the end of the tunnel. I won't bore you with a list of my symptoms right now but suffice to say they are very similar to the ones you reported in your previous posts, though with perhaps more of a cognitive deficit. Intriguing progress in the last few days though. We'll see if it continues, but your posts have given me a lot of hope, and I thank you for that!
Posted 16 June 2015 - 08:07 PM
Thanks for the quick reply! I am actually met/met for the val158met variation (against all odds), and I still get crazy fatigue and brain fog from methyl donors, though maybe it takes longer for this overload to occur since my COMT enzyme is less active.
I've been resetting methylation with niacin/niacinamide the past few days (assuming that's not a myth) and will try adding a low dose of methyl folate back in, along with some non-methyl b12. Any problem with cyanocobalamin in your opinion?
Recently I decided to give iron supplements a shot on the off chance I was deficient. I haven't been tested for iron levels and know it's not advisable to mess around with unnecessarily, but I was a bit desperate and figured I'd only continue if I noticed a benefit. Oh man, what a difference in terms of cognition and energy. I believe you said in an earlier post that you noticed a similar benefit from iron.
Anyway, between the iron and cutting way back on my methyl donors, I believe I am seeing a light at the end of the tunnel. I won't bore you with a list of my symptoms right now but suffice to say they are very similar to the ones you reported in your previous posts, though with perhaps more of a cognitive deficit. Intriguing progress in the last few days though. We'll see if it continues, but your posts have given me a lot of hope, and I thank you for that!
The problem with cyano-B12 is that it can only be absorbed in the gut, which reduces the absorption rate to 1 %. Hydroxo and methyl-B12 can be absorbed sublingually which gives it an absorption rate of approximately 20 %. It is, in other words, difficult to get enough cyano-B12 into your body without injecting it intravenously.
Iron can make a large difference for your well-being, but beware - if the effects are immediate (within an hour or two) it may have to do with the effects of free radicals (breaking down the instable enzyme methionine synthase, re-routing methylfolate towards BH4 production and thereby increasing dopamine) rather than increasing iron stores in the body.
I'm curious though - have you noticed any observable signs or other symtoms in addition to your cognitive symptoms, like skin changes, infections, itching or such? It would be interesting to see a summary of all the symptoms you are experiencing
Posted 16 June 2015 - 10:18 PM
The problem with cyano-B12 is that it can only be absorbed in the gut, which reduces the absorption rate to 1 %. Hydroxo and methyl-B12 can be absorbed sublingually which gives it an absorption rate of approximately 20 %. It is, in other words, difficult to get enough cyano-B12 into your body without injecting it intravenously.
Iron can make a large difference for your well-being, but beware - if the effects are immediate (within an hour or two) it may have to do with the effects of free radicals (breaking down the instable enzyme methionine synthase, re-routing methylfolate towards BH4 production and thereby increasing dopamine) rather than increasing iron stores in the body.
I'm curious though - have you noticed any observable signs or other symtoms in addition to your cognitive symptoms, like skin changes, infections, itching or such? It would be interesting to see a summary of all the symptoms you are experiencing
As to my symptoms, I have a diagnosis of ADHD-PI, though the emerging concept of Sluggish Cognitive Tempo (SCT) is probably more applicable. It is nothing recent--I've had lifelong issues with attention, focus, working memory, mental fatigue, sluggish processing, malaise, amotivation, asociality, etc. It runs in my family, too, so seems as genuine a case of ADHD-PI/SCT as you could find.
I am now interested in the idea that I may have had life-long low or borderline low iron, maybe a genetic predisposition to such, though I'm not going to assume anything. In some ways it would make sense: I've always had extra pale skin, fatigue easily, out of breath easily, etc. I remember distinctly having a lot less stamina than my friends as a child. In more recent years I have also noticed a tendency to bruise, and there are times when physical activity causes me to feel dizzy or generally unwell. These things seem in line with some of the iron deficiency symptoms I've read about. And, there are at least a couple of studies showing a strong association between ADHD and low iron status.
When I began iron supplementation, the effects were quite rapid. I feel more energetic, less fatigued, though time will tell on that. Also, my coloring appears affected. My hands for example seem to have a deeper and more reddish hue than normal.
I'm skeptical, and am prepared to be disappointed. It wouldn't be the first time. However, it is an interesting turn of events, worth exploring.
Your comment about the potential effect of free radicals is interesting. What are the signs that this would be the case? Is it at least feasible that my life-long issues could be related, at least in part, to iron status?
Posted 16 June 2015 - 11:47 PM
As to my symptoms, I have a diagnosis of ADHD-PI, though the emerging concept of Sluggish Cognitive Tempo (SCT) is probably more applicable. It is nothing recent--I've had lifelong issues with attention, focus, working memory, mental fatigue, sluggish processing, malaise, amotivation, asociality, etc. It runs in my family, too, so seems as genuine a case of ADHD-PI/SCT as you could find.
I am now interested in the idea that I may have had life-long low or borderline low iron, maybe a genetic predisposition to such, though I'm not going to assume anything. In some ways it would make sense: I've always had extra pale skin, fatigue easily, out of breath easily, etc. I remember distinctly having a lot less stamina than my friends as a child. In more recent years I have also noticed a tendency to bruise, and there are times when physical activity causes me to feel dizzy or generally unwell. These things seem in line with some of the iron deficiency symptoms I've read about. And, there are at least a couple of studies showing a strong association between ADHD and low iron status.
When I began iron supplementation, the effects were quite rapid. I feel more energetic, less fatigued, though time will tell on that. Also, my coloring appears affected. My hands for example seem to have a deeper and more reddish hue than normal.
I'm skeptical, and am prepared to be disappointed. It wouldn't be the first time. However, it is an interesting turn of events, worth exploring.
Your comment about the potential effect of free radicals is interesting. What are the signs that this would be the case? Is it at least feasible that my life-long issues could be related, at least in part, to iron status?
Interesting. Is there something that can reduce or remove your symptoms temporarily, like supplements or exercise? Have you tried any medication, like Ritalin?
Iron deficiency can cause ADD/SCT-like symptoms, and it can make existing ADD/ADHD/SCT worse. If you want to be sure if iron or other deficiencies plays a part in your symptoms, get a doctor to do some blood tests on you (including at least hemoglobin, iron, ferritin, B12, folate, TSH, calcium).
The noticeable effects from treating an iron deficiency comes over days or weeks, while the energizing effects from free radicals can (in my experience) come in an hour or so, lasting a few hours before crashing down into fatigue again. I read about this last summer but can unfortunately not remember the source.
EDIT: It is feasible that your symptoms are iron-related, but it is important to remember that life-long symptoms are usually not products of a nutritional deficiency. It's more likely to be caused by genetics. This said, as mentioned above, an existing condition may become worse if your iron levels are low.
Edited by Chadwick, 16 June 2015 - 11:59 PM.
Posted 17 June 2015 - 12:43 AM
Interesting. Is there something that can reduce or remove your symptoms temporarily, like supplements or exercise? Have you tried any medication, like Ritalin?
Iron deficiency can cause ADD/SCT-like symptoms, and it can make existing ADD/ADHD/SCT worse. If you want to be sure if iron or other deficiencies plays a part in your symptoms, get a doctor to do some blood tests on you (including at least hemoglobin, iron, ferritin, B12, folate, TSH, calcium).
The noticeable effects from treating an iron deficiency comes over days or weeks, while the energizing effects from free radicals can (in my experience) come in an hour or so, lasting a few hours before crashing down into fatigue again. I read about this last summer but can unfortunately not remember the source.
I take Vyvanse, without which I cannot fathom how I'd get through my work days, though I like to hope that this is not permanent. Vyvanse helps my cognition a bit but is mainly useful for mood, wakefulness, and motivation, and doesn't get me nearly where I need to be cognitively. Modafinil is probably the most effective thing I have ever tried for my cognition, and I substitute it for Vyvanse sometimes when I have it. I have tried many, many supplements with varying levels of success and consistency, but those affecting the glutaminergic system seem to be the most effective for me, including l-glutamine, l-glutamic acid, and NAC, though I haven't noticed much effect from sarcosine. When I first took l-glutamic acid I thought I was cured, but the effects diminished over a few days and while I still notice an effect when I take it occasionally, it is not the same. I can also relate to your observation of symptoms diminishing during hangovers. I have noticed this effect many times. Considering my responsiveness to other glutaminergic substances, it would make sense if the hangover effect, at least for me, were due to some kind of NMDA receptor rebound or increased glutamate, but that's pure speculation. I suspect that the great effect I get from modafinil is glutamate-related as well, which I believe is in line with the accepted wisdom about modafinil's mechanism of action.
The iron supplementation over the last few days has felt like as big of a game changer as any I have ever experienced, and it seems to be increasing instead of subsiding. My job is relatively mentally rigorous so I feel I am very sensitive to effects on my cognition. I had one of the best days today that I have had in a while. I hope like hell it's not a temporary effect such as the free radical effect you describe. I haven't experienced a crash or rebound of any kind, but time will tell. As I said, I've been disappointed before.
A quick google revealed a study stating that iron is important in the regulation and secretion of glutamate: http://ajpcell.physi...t/288/5/C1117. I haven't given it a close read, and I'm not knowledgeable enough about biology or physiology to really eyeball it accurately, but it sure looks like it could be an interesting puzzle piece considering my history of success with glutaminergic substances.
Posted 17 June 2015 - 04:25 PM
EDIT: It is feasible that your symptoms are iron-related, but it is important to remember that life-long symptoms are usually not products of a nutritional deficiency. It's more likely to be caused by genetics. This said, as mentioned above, an existing condition may become worse if your iron levels are low.
No doubt. I share your skepticism, and I have never had a doctor mention my iron levels though I'm sure it has been tested in various routine bloodwork in the past. However, I read somewhere that blood tests often only test for ferritin levels and not transferrin levels, and that sometimes ferritin levels may show up as normal whereas a transferrin test would reveal an iron deficiency.
Also, it's not clear why I would have an iron deficiency, as my diet has always been reasonable, if not stellar. Perhaps I have a genetic variation that affects iron metabolism. There appear to be a few SNP's that research has shown to be correlated with ferritin or transferrin levels, though my 23andme report does not appear to include most of the ones I have checked for. I may try digging more into this.
The iron-glutamate connection is fascinating to me. According to the study I cited before, iron deficient rats have been shown to have significantly lower serum glutamate and impaired behavioral function. The study notes that it is an open question whether iron levels affect the level of glutamate in the brain specifically, but it seems like a good possibility. According to the study, it all comes down to the iron-dependent enzyme cytosolic aconitase, which is suspected to affect glutamate production for various reasons.
An iron deficiency and resulting glutamate deficiency would elegantly connect all of the dots: 1) my physical symptoms, 2) my cognitive symptoms, 3) my marked response to glutamic acid and modafinil, 4) the fact that dopamine doesn't effectively treat my cognitive issues, and 5) the marked benefits I have received from iron supplementation so far for all of my symptoms.
Or maybe I'll be back to the drawing board in a week.
I'm still convinced that methyl folate has a role to play as well considering my homozygous C667T mutation, though I'm afraid to add it back in yet because of the brain fog it has caused recently. That will be my next experiment. Anyway, thanks for listening and for your comments!
Posted 26 June 2015 - 12:42 PM
Hi Kingsley, can you share what brand and dosage of iron that you've been taking? I share a lot of your symptoms and am interested in giving iron a try.
Hello,
I have been using Nature Made Iron 65 mg, which is ferrous sulfate, once a day. Remember that it is not wise to supplement iron absent a known iron deficiency, as it can be toxic. I do not plan to take it long term without having my iron levels checked.
Posted 07 July 2015 - 10:20 PM
Hello, I have yet to read the most recent updates, but I'd like to voice a thought before I do. I'd like to see how many people have felt this effect. For those who have, it would be nice for each to report in their own words what the experience is like. What is its duration and how was it activated.
I think a great way to describe the experience would be for each person to submit themselves to a fifteen minute picture activated writing prompt. I plan to drink heavily tomorrow, thereby producing the nootropic hangover. Hopefully I will remember to jump over here to write a few paragraphs on my experience. I do not advise doing this...
Lately, I have been having success battling depression and feeling hints of the nootropic hangover simply by sleeping well, eating well, and lifting well. In addition, I have been regularly taking:
B complex
Fish oil
NAC (2000 mg per day)
Low carb diet
Multivitamin.
The crazy focus and strange pattern-seeing mind of the nootropic hangover seems to be coming back somewhat, but I know there is a huge leap between sober cognition and that cognition. Soon, I will be taking Bacopa, Ashwhaganda, an activated B12, CoQ10, and Magnesium Threonate. I'll update then.
Lastly, because the hangover effect can do damage not only to the brain but to the liver, I'll be taking TUDCA on Friday, a day after the hangover effect. Still, I have yet to soberly reattain that mind state, though I have come close at times. It's become an obsession of mine.
Edited by Apprentice_Bob, 07 July 2015 - 10:49 PM.
Posted 08 July 2015 - 03:50 AM
Very interesting thread. Any updates on your progress, Chadwick? Is your regimen still effective?
I relate to many of the symptoms that you described in your original posts and have experimented with methyl donors. I am homozygous for the MTHFR C667T mutation, so by all rights I should benefit greatly from methyl folate and related supplements. In the beginning I had some success, but now methyl folate, methyl b12, and SAM-E all put me into an absolute brainless stupor following a brief rush of energy. Each one will do this to me on its own even in the absence of the others.
It's funny--all the overmethylation symptoms you read about online relate to overstimulation. You rarely hear about methyl donors causing brain-dead zombie syndrome. I'd kill for some overstimulation!
Anyway, due to my genetics it seems that methyl donors really should have a place in my regimen if I can just figure out how to benefit from them. You seem to have found a good balance. How's it going for you?
Anyone else having success with methyl donors? Has anyone else experienced insane brain fog on them?
I do just fine with an active B complex, methionine, and an extra methylcobalamin sublingual spray, extra 300 mg pantethine. No brain fog. TMG and SAMe will do odd things to me though, nothing consistent so I don't even try them anymore.
You do not want overstimulation. Everything in your environment will just overwhelm you and shut you down, if not trigger a meltdown. Imagine a panic attack turned inward, multiply that by 10.
You need "brain energy" without caffeine-like stimulants? Do coQ10 (minimum 100 mg but no more than 300 mg spaced out with food), extra 100 mg riboflavin, 500 mg to 1 gram creatine, carnitine, citrulline malate, ribose, pantethine (minimum 300 mg), taurine.
That combo will perk up your mitochondrial energy production/transport.
Don't neglect your electrolytes (cal, mag, potas, lithium, etc) or your other minerals.
Edited by Duchykins, 08 July 2015 - 03:50 AM.
Posted 08 July 2015 - 04:06 AM
No doubt. I share your skepticism, and I have never had a doctor mention my iron levels though I'm sure it has been tested in various routine bloodwork in the past. However, I read somewhere that blood tests often only test for ferritin levels and not transferrin levels, and that sometimes ferritin levels may show up as normal whereas a transferrin test would reveal an iron deficiency.
Also, it's not clear why I would have an iron deficiency, as my diet has always been reasonable, if not stellar. Perhaps I have a genetic variation that affects iron metabolism. There appear to be a few SNP's that research has shown to be correlated with ferritin or transferrin levels, though my 23andme report does not appear to include most of the ones I have checked for. I may try digging more into this.
The iron-glutamate connection is fascinating to me. According to the study I cited before, iron deficient rats have been shown to have significantly lower serum glutamate and impaired behavioral function. The study notes that it is an open question whether iron levels affect the level of glutamate in the brain specifically, but it seems like a good possibility. According to the study, it all comes down to the iron-dependent enzyme cytosolic aconitase, which is suspected to affect glutamate production for various reasons.
An iron deficiency and resulting glutamate deficiency would elegantly connect all of the dots: 1) my physical symptoms, 2) my cognitive symptoms, 3) my marked response to glutamic acid and modafinil, 4) the fact that dopamine doesn't effectively treat my cognitive issues, and 5) the marked benefits I have received from iron supplementation so far for all of my symptoms.
Or maybe I'll be back to the drawing board in a week.
I'm still convinced that methyl folate has a role to play as well considering my homozygous C667T mutation, though I'm afraid to add it back in yet because of the brain fog it has caused recently. That will be my next experiment. Anyway, thanks for listening and for your comments!
Whoa! Iron and glutamate have a relationship, who knew! Can you give me a list of the studies you found about this, just their titles or something and I'll do the rest.
I'm now wondering if I can lower extracellular glutamate by lowering my iron somehow. I am on the opposite side of the glutamate spectrum. I've always been pretty strong in iron for no apparent reason, but I only noticed this when I was in the Army and every time they came round to get blood donations, more than half the volunteers were sent back because their iron was too low. I was never sent back and frequently was the only female in my company that they would take blood from, all others didn't have enough iron. Blood tests repeatedly confirmed this 5 and 10 years later. This was really useful knowledge because it prevented me from making myself sick with unnecessary iron in multivitamins.
Posted 08 July 2015 - 01:22 PM
Whoa! Iron and glutamate have a relationship, who knew! Can you give me a list of the studies you found about this, just their titles or something and I'll do the rest.
I'm now wondering if I can lower extracellular glutamate by lowering my iron somehow. I am on the opposite side of the glutamate spectrum. I've always been pretty strong in iron for no apparent reason, but I only noticed this when I was in the Army and every time they came round to get blood donations, more than half the volunteers were sent back because their iron was too low. I was never sent back and frequently was the only female in my company that they would take blood from, all others didn't have enough iron. Blood tests repeatedly confirmed this 5 and 10 years later. This was really useful knowledge because it prevented me from making myself sick with unnecessary iron in multivitamins.
Hello:
I based my glutamate-iron speculation on a single study by the name of "Iron alters glutamate secretion by regulating cytosolic aconitase activity" and one or two studies mentioned in that article. While the study shows a connection between glutamate and iron, it is far from clear whether the normal range of iron in the human body has any effect on glutamate levels in the body or brain. It is pretty much pure speculation at this point and I don't claim any particular knowledge of physiology.
Posted 08 July 2015 - 01:39 PM
Kingsley, would you mind describing the hangover effect qualitatively. A short paragraph, perhaps a number of bullet points. Then, if you wouldn't mind, describe your current levels of cognition.
Also, if you ever happen to become re-hangovered, it'd be nice to hear from you in that state. I find that the way I communicate changes drastically, whether by type or speech.
Posted 08 July 2015 - 01:47 PM
Hello, I have yet to read the most recent updates, but I'd like to voice a thought before I do. I'd like to see how many people have felt this effect. For those who have, it would be nice for each to report in their own words what the experience is like. What is its duration and how was it activated.
I think a great way to describe the experience would be for each person to submit themselves to a fifteen minute picture activated writing prompt. I plan to drink heavily tomorrow, thereby producing the nootropic hangover. Hopefully I will remember to jump over here to write a few paragraphs on my experience. I do not advise doing this...
Lately, I have been having success battling depression and feeling hints of the nootropic hangover simply by sleeping well, eating well, and lifting well. In addition, I have been regularly taking:
B complex
Fish oil
NAC (2000 mg per day)
Low carb diet
Multivitamin.
The crazy focus and strange pattern-seeing mind of the nootropic hangover seems to be coming back somewhat, but I know there is a huge leap between sober cognition and that cognition. Soon, I will be taking Bacopa, Ashwhaganda, an activated B12, CoQ10, and Magnesium Threonate. I'll update then.
Lastly, because the hangover effect can do damage not only to the brain but to the liver, I'll be taking TUDCA on Friday, a day after the hangover effect. Still, I have yet to soberly reattain that mind state, though I have come close at times. It's become an obsession of mine.
I have regularly felt the hangover nootropic effect. I would describe it as a day-long brightened mood with more mental energy, and a feeling that my thoughts are "busier" than usual (not strong enough to call "racing thoughts"). This would seem consistent with increased glutamate release, which I have read is implicated in hangovers. It would also suggest a "true" nootropic effect, as many nootropics are thought to affect the glutamate system of receptors, i.e. nmda and ampa receptors.
I am also obsessed with achieving something approaching this mental state consistently and have tried many substances targeting the glutamate system. Boosting glutamate via l-glutamic acid and/or l-glutamine was extremely effective for me but only temporarily, and some will say that these substances carry a risk of excitotoxicity, of which I'm not convinced. The most consistent nootropics for me so far, after getting my basic vitamins and minerals in place, have been NAC and sarcosine, though they can be hit or miss, especially sarcosine. Tolerance really is the bane of my existence.
Posted 08 July 2015 - 02:09 PM
I have regularly felt the hangover nootropic effect. I would describe it as a day-long brightened mood with more mental energy, and a feeling that my thoughts are "busier" than usual (not strong enough to call "racing thoughts"). This would seem consistent with increased glutamate release, which I have read is implicated in hangovers. It would also suggest a "true" nootropic effect, as many nootropics are thought to affect the glutamate system of receptors, i.e. nmda and ampa receptors.
I am also obsessed with achieving something approaching this mental state consistently and have tried many substances targeting the glutamate system. Boosting glutamate via l-glutamic acid and/or l-glutamine was extremely effective for me but only temporarily, and some will say that these substances carry a risk of excitotoxicity, of which I'm not convinced. The most consistent nootropics for me so far, after getting my basic vitamins and minerals in place, have been NAC and sarcosine, though they can be hit or miss, especially sarcosine. Tolerance really is the bane of my existence.
Yes, same here. Although, I haven't had major success with any set of nootropics. There have been moments... fleeting and insubstantial, where I seemed to feel like I had finally arrived. I struggle between assigning to myself a sickness, and to supplements a cure, and to myself normalcy and to supplements an enhancement.
The nootropic hangover does not feel nootropic. It is the only effect which actually seems to raise my IQ, rather than my ability to function. But, I have had serious and abnormal twinges of pain in my head from the effect, and I can't imagine that it is at all sustainable. You feel extremely on edge at times, senses can become very heightened to the point of intolerance. I personally become very intense and outspoken, but also calm and subdued. Lol. It's a great experience, one that I have come to live for, even if I only experience it every few months. You can achieve so much during those days of enhancement. The hope is that those days won't incur any serious damage. The hope is also that sober self can get to a position with a potential such that hangover self can move a lot of weight in one day, if you see what I am saying. ... I don't want to drag this on, but I have thought about this for more time than most things. I could pm you if you are interested.
Bottom line: I will let you know how Bacopa, Q10, and the other ones. I may buy Dihexa. It reminds me the hangtropic effect.
Posted 19 July 2015 - 04:54 PM
Posted 20 July 2015 - 09:19 AM
You should have seen some benefit from methylB12 but you said you felt better on hydrxyB12. Any ideas why ?
I'm homozygote for MTRR A664A rs1802059 AG +/+ and hetero for a few others and I wonder if I should include hydroxy of dibencozide in addition to methyl. Thanks.
It seems like methylation isn't a big problem for me, but low BH4 synthesis is. Methyl B12 can reduce BH4 synthesis futher, which is the opposite of what I want. Hydroxocobalamin doesn't affect it at all. The reason I take B12 at all is that I want to avoid "methyl trapping", which is when methyl folate uses up all the B12 in the cells. The low intracellular B12 will then cause the cells to expel folate.
Can you link to the study that shows that methylcobalamin can reduce BH4 synthesis?
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