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No libido since forever, A1298C positive.

pab

Messages
11
Hello

since many years (around 10 for sure) I've been suffering from ZERO libido. I'm 26yo otherwise healthy guy.
It's clear that I have low dopamine and possibly serotonine problems going by the way I behave and feel etc but also confirmed but super low catecholamin test.
katecholaminy.thumb.jpg.39a2cc166580a4b6ba5a6394badc0722.jpg



Now - I just found out I have a heterozygous mutatation A1298C.
Having read (scarce) info online stating that this mutation is connected to BH4 and therefor to neurotransmitters I'm quite positive this might be the root cause of my problems which for every doctor I saw (+100 easily) have been incomprehensible.

I've tried countless drugs and supplements and not only they didn't cure me but normally there has always been absolutely no effects whatsoever, like sugar placebo pills. Be it a dopamine agonist, dopamine antagonist, testosterone injection, thyroid hormones etc.


Could you point me in the right direction? Where do I start?
 

Glycon

World's Most Dangerous Hand Puppet
Messages
299
Location
ON, Canada
Do you have the C677T mutation as well? Other mutations?

(I ask because, from what I understand, there isn't really any evidence that your mutation does much of any significance on its own.)

Having read (scarce) info online stating that this mutation is connected to BH4 and therefor to neurotransmitters I'm quite positive this might be the root cause of my problems

Clearly you haven't read hard enough, since not even the experts are "quite positive" about anything this specific in relation to MTHFR's clinical significance.
 
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alicec

Senior Member
Messages
1,572
Location
Australia
Now - I just found out I have a heterozygous mutatation A1298C.
Having read (scarce) info online stating that this mutation is connected to BH4 and therefor to neurotransmitters I'm quite positive this might be the root cause of my problems which for every doctor I saw (+100 easily) have been incomprehensible.

The online stuff about this SNP is mainly nonsense. This mutation is very common - millions of people have it and they are not all struggling with neurotransmitter problems, nor is the SNP the cause of your problems.

The SNP simply causes a moderate slowing of enzyme activity. Even +/+ has only a modest effect; +/- even less so. Supplementation with the enzyme cofactor B2 may be helpful in stimulating a sluggish enzyme. Maybe the product of the reaction, ie methylfolate, could be helpful.

The stuff about BH4 is based on a misreading of research. There is no link between this gene variant and BH4 production.

There is an indirect link between methylfolate and BH4. Methylfolate is a peroxynitrile scavenger and so has a BH4 sparing effect.
 

hixxy

Senior Member
Messages
1,229
Location
Australia
@alicec That doesn't mean that the enzyme is not underfunctioning for reasons unrelated to genetics, so methylation treatment may still be helpful ... or not.

Naviaux's CDR and the recent metabolomic findings for ME are a pretty good example of how that might happen.
 

alicec

Senior Member
Messages
1,572
Location
Australia
That doesn't mean that the enzyme is not underfunctioning for reasons unrelated to genetics, so methylation treatment may still be helpful ... or not.

Absolutely. The fact that so many people on PR get some benefit from active B12/folate suggests that these pathways are adversely impacted by the disease - as indeed Naviaux's study shows.

I was pointing out though that this SNP is not the cause of low libido or indeed of health problems in general.
 
Messages
15,786
Yeah, if someone only has MTHFR A1298C +/-, they're doing better than most other human beings on that gene :p It reduces enzyme function by about 17%, whereas enzyme function is reduced by approximately 30% on average in the general population due to the various MTHFR mutations, primarily A1298C and/or C677T.
 

pab

Messages
11
@Glycon @alicec @hixxy @Valentijn
Many thanks for your input!


Do you have the C677T mutation as well? Other mutations?

(I ask because, from what I understand, there isn't really any evidence that your mutation does much of any significance on its own.)
No, it's the only one.




I'm still digesting this and I understand I might have jumped the gun assuming it's the root cause of my misery.

Anyway, it's the only lead I have at the moment and just for the sake of trying I'd like to see what happens if I get on the right supplementation protocol.

There seems to be a lot of confusion on-line and doctors here in Poland seem to be pretty ignorant about all this...

What would be the smartest way of designing my supplemention protocol?
Is there a list of recommended doses and products? I'm super new to this products, almost none of them available in Poland so will need to order from iherb/US/amazon...
 

alicec

Senior Member
Messages
1,572
Location
Australia
I'm still digesting this and I understand I might have jumped the gun assuming it's the root cause of my misery.

Yes sorry to disappoint you but it's best not to get caught up in false beliefs.

This doesn't mean that activeB12/folate might not be helpful. They may well be since they influence neurotransmitter production. Sorry I can't be more specific about low libido - don't know much about it.

Here is a post I wrote about introducing these active vitamins. You need to realise that many people with ME/CFS are very sensitive to these vitamins and need to proceed very cautiously and the post was written for such a person. You perhaps may not have this problem since I understand you do not have this disease. Still don't rush into things too quickly. These active vitamins can be very powerful.
 

PeterPositive

Senior Member
Messages
1,426
A couple of things that can help with libido is taking high dose zinc, for example 20-30mg/day and Ashwagandha, in particular the KSM66 extract (found in many products such as Jarrow etc...) at 600-900mg/day.

B vitamins can help too, especially high dose B12, but as others have suggested it is best to start with a low dose, see how it goes. then increase it gradually.

These 3 together should help libido quite a bit.
 

pab

Messages
11
A couple of things that can help with libido is taking high dose zinc, for example 20-30mg/day and Ashwagandha, in particular the KSM66 extract (found in many products such as Jarrow etc...) at 600-900mg/day.

B vitamins can help too, especially high dose B12, but as others have suggested it is best to start with a low dose, see how it goes. then increase it gradually.

These 3 together should help libido quite a bit.

What I tried to tell in my first post was that nothing and I tried almost everything (suppements, herbs, rx stuff) helps with my libido. Ate tons of zinc, ashwaganda and plethora of other stuff. Nothing can give me even the slightest sexual drive... Clearly something got "switched off" and no-one knows what and how to revert it.

The only logical lead I have is a mess within my neurotrasmitters network, mainly dopamine. Those articles connecting a1298c to dopamine and serotonine sound very "possible" in my case, however as you guys say it may be just correlation not causation.

@alicec Thank you for the link. That's exactly what I need! As I will be ordering my stuff from the US, due to shipping time to Poland I'd prefer to make good decisions buying stuff :)
 

Crux

Senior Member
Messages
1,441
Location
USA
Have you ever had iron, ferritin, etc. checked?
One of the symptoms of iron overload is loss of libido.
 

pab

Messages
11
@Crux Of course I have. Spent fortune on tests of all kinds. I'm a healthy folk for all doctors. The only abnormality which can be proved in an actual test are low catecholamins + intestinal dysbiosis which surely contribute somehow to all this but certainly is not a root cause.
 

JES

Senior Member
Messages
1,318
Anyway, it's the only lead I have at the moment and just for the sake of trying I'd like to see what happens if I get on the right supplementation protocol.

As @Valentijn wrote, MTHFR on average is reduced by 30% in general population, these mutations are that common. So having heterozygous MTHFR and 17% reduction does not explain your symptoms.

But anyway, it doesn't exclude that neurotransmitters can be the problem. If you want to influence neurotransmitters efficiently, then medication is usually the way to go. Bupropion is an antidepressant which prevents dopamine re-uptake, people suffering from SSRI induced sexual dysfunction have had success in reversing symptoms with bupropion. Another safe medication to try is LDN, it does increase my libido and I've read similar reports from other people.
 

pab

Messages
11
@JES Two things:
1) in my pursuit of normal life I tried both dopamine agonist and antagonist and neither caused anything noticable...This is a clear sign that something is seriosuly wrong. You can't take antipsychotics like tic-tacs, can you?
2) at the moment I'm working on improving the sensitivity of my receptors (uridine, sulbutiamine + different racetams). Hope that after 2-3 months when I'm off my cycle and therefore my dopamine is higher - something will be noticable,
 

Dufresne

almost there...
Messages
1,039
Location
Laurentians, Quebec
What I tried to tell in my first post was that nothing and I tried almost everything (suppements, herbs, rx stuff) helps with my libido. Ate tons of zinc, ashwaganda and plethora of other stuff. Nothing can give me even the slightest sexual drive... Clearly something got "switched off" and no-one knows what and how to revert it.

Do you have ME/CFS?

Was anything out of the ordinary going on in your life when you lost your libido (health problems, stress, trauma, etc.)?
 

pab

Messages
11
Do you have ME/CFS?

Was anything out of the ordinary going on in your life when you lost your libido (health problems, stress, trauma, etc.)?

No, I don't have ME/CFS. I may not have energy levels you'd expect from a 27yo but I'm doing pretty well. I'm working in a fast-paced environment which requires a lot of multitasking and being cognitively sharp and I'm doing well. Trying to be at least 4 times a week at the gym, have an over-average physique (though it's quite obvious I need more time and efforts than others to build muscle/lose fat).

Although no obvious event or situation, at least that I remember, I'd say the most probable answer would be: took accutane. There is quite a few folks reporting similar side effects to mine. However, it seems that some of them get better with time or some supplementation/drugs. I don't.

Been eating super healthy (no processed food since many years), alcohol twice a year max, no drugs, no nicotine, sleeping 7-8 hours.
 

JES

Senior Member
Messages
1,318
@JES Two things:
1) in my pursuit of normal life I tried both dopamine agonist and antagonist and neither caused anything noticable...This is a clear sign that something is seriosuly wrong. You can't take antipsychotics like tic-tacs, can you?
2) at the moment I'm working on improving the sensitivity of my receptors (uridine, sulbutiamine + different racetams). Hope that after 2-3 months when I'm off my cycle and therefore my dopamine is higher - something will be noticable,

Bupropion actually works very differently than a dopamine agonist, even though both technically increase dopamine levels. It's also not in the same class as antipsychotics, which I would agree can be dangerous medications, whereas bupropion is one of the most commonly prescribed antidepressants in the US. In Europe it might be harder to get a prescription for it, as in some countries it's mainly prescribed as a smoke cessation aid.
 

TrixieStix

Senior Member
Messages
539
....not even the experts are "quite positive" about anything this specific in relation to MTHFR's clinical significance.

I agree. The MTHFR thing in my opinion is over hyped, especially by the Naturopathic community whose treatment consists of purchasing lots of supplements from them. However there are definitely known and well researched medical effects of MTHFR mutations such causing pregnancy complications like repeated miscarriages. This is something an OBGYN will test for if suspected.

I found out a couple years ago from my 23andme test that I am what is referred to as "Compound Heterozygous for MTHFR" andit is touted as one of the more potentially serious mutation combos. However after doing weeks of research online I came to the conclusion that getting my Homocysteine level tested should be adequate enough to know whether of not I need to be worried about my MTHFR status. As someone posted above, having a mutation/s does not guarantee problems it just means your methylation cycle could be impacted to a degree. I can't find the webpage I originally found talking about MTHFR and Homocysteine and using it as a test to see if your undermethylating, etc. Here is another medical article I found that discusses it at length...

"The MTHFR mutations appear to be medically irrelevant, so long as an individual’s homocysteine level is normal. Therefore, it should be the homocysteine level, not the MTHFR genetic status, that is tested in patients with or at risk for blood clots, atherosclerosis, or pregnancy complications." (link below)

http://circ.ahajournals.org/content/111/19/e289

After learning all of this I got my Homocysteine level tested and it was 10 which from my research is an ideal number.
 
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Messages
15,786
I found out a couple years ago from my 23andme test that I am what is referred to as "Compound Heterozygous for MTHFR" andit is touted as one of the more potentially serious mutation combos.
One additional note: compound heterozygous status can't be determined from 23andMe results, with the possible exception of when you know one or both parents' status as well. 23andMe puts everything in alphabetical order, and never indicate which alleles are on the same strand.
 

TrixieStix

Senior Member
Messages
539
One additional note: compound heterozygous status can't be determined from 23andMe results, with the possible exception of when you know one or both parents' status as well. 23andMe puts everything in alphabetical order, and never indicate which alleles are on the same strand.

A person's 23andme raw data when uploaded to an online service such as "Promethease" or "Genetic Genie"does indeed tell you your MTHFR status. Mine shows I am "Compound Heterozygous" using just my own raw data alone as neither of my parents have been tested.

I myself am

rs1801133(C;T) https://www.snpedia.com/index.php/Rs1801133

rs1801131(A;C) https://www.snpedia.com/index.php/Rs1801131(A;C)

"MTHFR 677CT + MTHFR 1298AC = a compound heterozygous mutation which is one mutation from two different parts of the gene"

http://mthfr.net/what-is-mthfr/2011/11/04/