Dopamine

[Daveman]

So this suggests another mechanism by which POIS may be treated i.e. the reduction of the histamine release upon orgasm by desensitisation treatment.
What I'm getting at here is that while it seems like we may all be suffering from different things because the treatments are so varied and seemingly different, it could all be the same thing - some ALDH mutation - in which case we should all take a bit of supplementary niacin and methionine no matter what else we're doing

It can't hurt and as Bruce Ames (a legendary Biochemist in UC Berkley) points out in http://chemistry.beloit.edu/Ordman/classes/cls/reading/Ames.pdf

"you can feed people niacin and raise NAD levels"

which reduces the effects of an ALDH transcription problem. Niacin may have the dual effect of 1) reducing histamine reserves that would be released in the brain during an O 2) increasing the effectiveness of a mutated gene-produced aldehyde dehydrogenase.

POIS sufferers may get a benefit from both 1 and 2.
There could also be many paths to POIS symptoms developing or becoming obvious including bacterial infection, systemic fungal infection, autoimmune illness etc. Depending on diet, lifestyle and degree of ALDH mutation, someone may always have POIS or have a latent POIS which they develop following a period of stress/illness.

Just a theory!
Has anyone tried SAMe versus l-methionine and what were the results?

Part of this was over on the Fungus infection thread, but this part is better asked here!

I'm not sure if I heard you say somewhere that Niacin may work better on some because their system "damage" is lesser advanced than in others. This could well be my case, being someone who has only recently developed POIS (well, 8 to 10 yrs), and so if it is genetic it has been latent.

But one feels as though there is damage being done over time. This lack of conversion or improper conversion of histamine does sound aggressive and damaging. So even if niacin doesn't really make you feel better, it sounds as though it would help a lot to prevent further damage from being done, until we at some point find a more precise "cure" for POIS.

Niacinamide daily then sounds like a good treatment for ALL of us, whether it reduces POIS symptoms or not, right?

[kurtosis]

Yeah, I think that we should all consider taking niacin or niacinamide daily rather than just on days where we're planning an O. This may yield a bigger long term improvement than just taking niacin on O days.

I don't think it's a good idea to supplement methionine every day but some supplementation every week may increase the levels of SAMe and help reduce histamine. Part of the problem is that L-methionine capsules contain a lot of methionine - 500mg.

Research using autistic kids suggests that NADH & D-Ribose may be a safe way to increase dopamine and increase SAMe without supplementary methionine. However, this may not be the case for those that eat a vegetarian diet which may not have adequate methionine. Garlic has plenty of it

This is why I don't believe the very expensive SAMe is required if someone already has a reasonable amount of methionine in their diet and is taking NADH. I believe that SAMe levels will rise accordingly, increasing methylation and reducing histamine in a more "natural" way.

NADH & Ribose both separately increase SAMe and therefore methylation which helps balance histamine. Taken together there may be additional benefit.

[nomore2013]

NOW brand has nadh w/d-ribose. i didnt know what that was. it is not enada nadh, but it says it has a stable and bioavailable release. it is not enteric coated, it is a capsule. but the reviewers say it work. so i dont know.

[kurtosis]

NOW brand has nadh w/d-ribose. i didnt know what that was. it is not enada nadh, but it says it has a stable and bioavailable release. it is not enteric coated, it is a capsule. but the reviewers say it work. so i dont know.

It's Panmol. Both panmol and enada are using a very similar process (involving chlorophyll) to get the NADH past the stomach where it would burn up. I think that the 20mg + ribose version of the Now Foods one would be fine. The 2 companies seem to be in a legal dispute so I don't think we should get into any discussion of which one is better except to say that they both appear similar.

I'll take some more ENADA nadh and ribose later today. As far as I'm concerned, it's rocket fuel. It's a gradual boost, not like a stimulant but the effects last much longer, for me anyway.

[kurtosis]

The COMT Gene, dopamine synthesis and metabolism and the use of COMT variations as a predictor for benefit derived from amphetamines
Fascinating article from the National Institute for Health http://www.nimh.nih.gov/science-news/2003/gene-enhances-prefrontal-function-at-a-price.shtml

23andme can show COMT gene variations so this stuff is testable.

[Nightingale]

Fantastic article kurtosis.  Makes me more interested in 23andMe.  I don't know all that much about it, how seriously should we consider them?  Obviously price is a factor

[kurtosis]

Fantastic article kurtosis.  Makes me more interested in 23andMe.  I don't know all that much about it, how seriously should we consider them?  Obviously price is a factor

Yeah, price is a factor. It would be great to compare COMT and all the histamine metabolism genes (methylation & ALDH) across all POIS sufferers. Classic multi-factorial statistical analysis to see how accurately a set of genes predict POIS. We only have POIS sufferers here so it's not ideal (false positives possible) but it would still be instructive.

[kurtosis]

Fantastic article kurtosis.  Makes me more interested in 23andMe.  I don't know all that much about it, how seriously should we consider them?  Obviously price is a factor

B_Daniel got a test recently that said he had a COMT impairment (under-methylating) leading to slow catecholamine clearance. It would be great to know
1) the val/met balance of his and our genes
2) whether other POIS sufferers have similar problems.

Perhaps he can comment when he gets the time.

[Nightingale]

I just realized, in the article they described how a particular variant of that gene combo led to decent cognitive performance until the most difficult tasks in their test.  This is currently a major issue of mine.  I don't have terrible attention/cognition until I'm in class at school or I'm looking at a blank word processor document trying to write a paper.  These demand a lot of "processing power" and are just when I "lock up"

[kurtosis]

Fantastic article kurtosis.  Makes me more interested in 23andMe.  I don't know all that much about it, how seriously should we consider them?  Obviously price is a factor

B_Daniel got a test recently that said he had a COMT impairment (under-methylating) leading to slow catecholamine clearance. It would be great to know
1) the val/met balance of his and our genes
2) whether other POIS sufferers have similar problems.

Perhaps he can comment when he gets the time.

By the way, anyone taking methionine, MSM, TMG or SAM-e to reduce their histamine levels: please make sure you're getting b3 and b6 also as your body needs extra b6 to deanimate the histamine and b3 to help convert the byproduct, an acetaldehyde into harmless acetic acid. This is why it's suggested people take b vitamins in complexes (even if they need more of some than others) because they act as cofactors in metabolic reactions which increase your requirement for other b-vitamins. Does that make sense?

[Nightingale]

Is it at all likely that sustained NADH supplementation could make you depressed?  Over the past 3 weeks I've become depressed, and the majority of that time I've been taking 10mg of NADH in the morning.  I also had a negative response from taking Wellbutrin at the start of those 3 weeks.  I'm thinking of asking my doc about going back on an SSRI, but I'm wary as they've never really seemed to help me and I do get side effects.  I have cut back on taking my Now B co-enzyme complex so as to not interfere with the NADH.  I just started taking my morning dose at mid day instead of foregoing it all together til my night dose.

I've been working out by lifting weights and doing some cardio, and I've been managing my stress fairly well with Clonipin.  It's just my mood has tanked.  It's not at a very serious point yet, but I am worried.

Only thing I can think of is that I have not been taking b12 for about a week and a half.  Just went out and got more.  That and that the weather has changed and winter is coming.  I have a Seasonal Affective Disorder lamp that I've had for many years, and use it diligently though.

Im afraid tinkering with my neurotransmitters with all these new meds I've tried has thrown my levels out of whack.  I may need that serotonin boost for a while..

[kurtosis]

Is it at all likely that sustained NADH supplementation could make you depressed?  Over the past 3 weeks I've become depressed, and the majority of that time I've been taking 10mg of NADH in the morning.  I also had a negative response from taking Wellbutrin at the start of those 3 weeks.  I'm thinking of asking my doc about going back on an SSRI, but I'm wary as they've never really seemed to help me and I do get side effects.  I have cut back on taking my Now B co-enzyme complex so as to not interfere with the NADH.  I just started taking my morning dose at mid day instead of foregoing it all together til my night dose.

I've been working out by lifting weights and doing some cardio, and I've been managing my stress fairly well with Clonipin.  It's just my mood has tanked.  It's not at a very serious point yet, but I am worried.

Only thing I can think of is that I have not been taking b12 for about a week and a half.  Just went out and got more.  That and that the weather has changed and winter is coming.  I have a Seasonal Affective Disorder lamp that I've had for many years, and use it diligently though.

Im afraid tinkering with my neurotransmitters with all these new meds I've tried has thrown my levels out of whack.  I may need that serotonin boost for a while..

Has the opposite effect on me but we're all different.
Given that you have other medication, anything is possible.


Are you taking methionine or SAMe?
NADH tends to make people LESS depressed (see the studies) so this would be an unusual side effect for you.
However, if the high-histamine theory is correct, you'd may need a methionine source to ensure that the serotonin levels rose as much as catecholamine levels (which NADH will primarily effect).

SAMe appears to have a serotonin boosting and histamine decreasing effect. That's why I take NADH and SAMe (or just another methionine source) together.
I don't believe you can take SAMe and an SSRI together (you can check with your doctor) so that could be the problem as there's a risk of serotonin syndrome. I tried SSRI's and the only benefit I got was less interest in having O's such that I didn't have one for 3 weeks and I did feel better I didn't consider that progress to be honest.

What I noticed from the NADH & SAMe combination is more energy and less allergies. Less scratching, itching and general signs of inflammation such as hives. I got similar results from L-methionine but it worked best when I felt energetic whereas SAMe seems to put me back on track even if I'm tired from working/exercising/whatever.

If you have SAD, are you supplementing vitamin D? Either by itself or taking something like cod liver oil?

[Nightingale]

I am taking methione 2x a week.  Since you are saying that NADH would affect catecholamine levels, maybe I am making more dopamine then normal and my serotonin levels are not keeping up/lowering.  I have had these pro-dopamine drugs give me issues recently.  I'm going to stop taking NADH until it's been tried by more people.

It really sucks so many potential treatments cause me issues, I can't take carnitine or tyrosene witout feeling bad side effects, not any supplement/herb that increases nitric oxide levels.

I have been supplementing with vitamin D for a long time since I was diagnosed with deficiency two years ago.

I'd consider taknig SAMe over an SSRI, I've honestly had enough of trying them out.  I'm going to see if methionine will boost my serotonin levels.  Not sure if you've seen any info on that kurtosis

[kurtosis]

I am taking methione 2x a week.  Since you are saying that NADH would affect catecholamine levels, maybe I am making more dopamine then normal and my serotonin levels are not keeping up/lowering.  I have had these pro-dopamine drugs give me issues recently.  I'm going to stop taking NADH until it's been tried by more people.

It really sucks so many potential treatments cause me issues, I can't take carnitine or tyrosene witout feeling bad side effects, not any supplement/herb that increases nitric oxide levels.

I have been supplementing with vitamin D for a long time since I was diagnosed with deficiency two years ago.

I'd consider taknig SAMe over an SSRI, I've honestly had enough of trying them out.  I'm going to see if methionine will boost my serotonin levels.  Not sure if you've seen any info on that kurtosis

I don't think the problem is NADH. THe problem is not enough methionine.

The body can produce SAMe from methionine but to produce sufficient amounts, it needs energy. NADH provides energy but you need more methionine to help it produce SAMe.
I'm taking SAMe every day so I'm guessing that someone taking methionine would need to do so every day also. I wasn't sure whether I was over/under methylating so I wanted to start slow but after the first few days convinced me methionine was working, I upped the dose, then switched to SAMe.

You shouldn't take methionine and SAMe together so you'll need to make a decision on either but I guess, to do what I'm doing, you'd need to take it every day.

[Nightingale]

After not taking NADH for 4 days now, I feel MUCH better.  I had been taking methionine 2x a week during that time.  I am going to enjoy a week or two of positive mood before I jeapordize it with anything else, but when I'm ready I have methionine and could easily find SAMe.

[kurtosis]

After not taking NADH for 4 days now, I feel MUCH better.  I had been taking methionine 2x a week during that time.  I am going to enjoy a week or two of positive mood before I jeapordize it with anything else, but when I'm ready I have methionine and could easily find SAMe.

What else are you taking? NADH may have interactions with any drugs that effect the synthesis or reuptake of catecholamines as it increases Tyrosine Hydroxylase.  It might just be a supplement but it has powerful affects on the levels of tyrosine hydroxylase which means that tyrosine is converted more efficiently and faster to dopamine when supplementing NADH.

This makes me feel great, there are lots of reasons why it might not work for you including existing medication, medication still in your system, all kinds of things.
I take SAMe every day now. It's about the equivalent of 3*200mg of TMG. Possibly a similar amount of methionine. It's difficult to calculate as I have increased ATP which would mean more SAMe created from methionine.

[LAPOISSE]

Hi,

it's great work you have done ; especially you Kurtosis ; thank you for digging with that scientific rigor ; ) ...By the way I think if there is any research program going on afer NORD funding is done, Kurtosis and other people in here, good with med and science research should be part of it...There has been so much work done in here ; it will be very helpfull not to start from zero.

Could we have a kind of resume of the dopamine research you have done ? It's kind complicated for me to extract information that I could share with my doc ; I'm not a scientist and my comprehension of this kind of stuff in english is limited.

Dopamine deregulation(as a cause or a consequence) make a lot a sense to me...It's involved in everything as I experience as a symptoms ans it matches really well with vitamine cure(C ; B6...)

The good thing in France is a can do blood test or any kind of test for free pretty much...So I wanna explore everything makes sense

[hurray]

I spent a while trying dopamine-related medications, hoping that they could alleviate my POIS:

piracetam
l-tyrosine
selegiline
wellbutrin
cabergoline
modafinil

There's probably a bunch more that I can't remember right now, most were a number of years ago.

They didn't ultimately do much for me, although in some cases they gave my brain a boost when I was out of POIS.

I'm currently taking Ritalin, with the help of my psychiatrist (40mg/day). This has been the most useful medicine so far by some distance, but for me it doesn't prevent or cure POIS.

I'm not suggesting that there isn't a link between POIS and dopamine, but various dopaminergic drugs didn't feel like they were doing much to fight my POIS. I would be very interested to see somebody reporting long-term success with this class of drugs, I believed for years that dopamine was the key to the POIS mystery.

[berhune]

I'm currently at that point, 'hurray.'  Taken by the idea that a prolactin surge after O significantly antagonizes dopamine, I've been trying to build a stack of supplements that help with the symptoms of my POIS.  Over the last two weeks, I've gained tentative relief from:

200mg NAC (N-Acetyl Cysteine) +
100mg Mucuna Pruriens +
a hot cup of green tea

The idea was, if POIS was indeed dopamine-related, to give the brain some L-Dopa for replenishment purposes.  The NAC and green tea (EGCG) were based on the tenuous belief that keeping the LD from oxidizing as long as possible was a good idea.

I chose the Mucuna because synthetic L-Dopa contraindications scare me.  I always eat an extremely healthy diet and get plenty of exercise, so I thought perhaps my body wasn't replacing the dopamine very quickly or efficiently on its own, therefore I wanted to get as close of a precursor to dopamine as possible (I decided against L-Tyrosine and L-Phenylalymine for this reason).

I only take the Mucuna two-three times per week, when I notice symptoms about 18-24h after O.  I don't like the idea of downregulating dopamine receptors or anything - cycling seems to be the way people best enjoy Mucuna for other reasons.

For what it's worth, I've always drank green tea but it's never helped my POIS on its own, but NAC alone gives me a feeling of mental relief no matter when I take it.  I've heard the words 'oxidative stress' elsewhere and would like to explore that avenue further as a way to relieve symptoms.

POIS has always been a serious problem for me.  I would always get cold sore outbreaks and nasty colds immediately after O, but the worst were the mental side effects.  God.  The brain fog and the awareness of being trapped in a slow-moving machine, lagging behind the rest of the world, was devastating in a job that required multitasking, precision, and eloquence.  Additionally, my motivation would flag significantly for personal projects during the approx. 5 days after orgasm.  It was astonishing how, after that period was exceeded with no O, I became sharper and sharper, and far more willing to get work done on my own.  I could only sustain the abstinence for so long before a NE would start the cycle again.  Cruel world.

Point is, for the past two Os, the NAC + Mucuna experiment has correlated with the reduction of my cognitive side effects.  I can get work done more effectively, but am very wary of overdoing it with dopamine.

[asdfdoc]

didn't help me much either

I tried adderall, methamphetamine (when I was young), ritalin, wellbutrin, strattera and modafinil.

Adderall relieved my symptoms for 4 hours only if I took it after O. Before O, as soon as I O, adderall effect is gone and I am sleepy.

Meth, same as adderall, just speedy as hell.

Ritalin, no help what so ever.

Wellbutrin, no help what so ever

Strattera, no help what so ever

modafinil, similar to adderall but to much weaker extent.


However, I do benefit from lexapro after O, main reason I think my POIS comes from serotonin problem. Adderall does affect serotonin system as well.

I also have social anxiety and ADHD...