NAD+ & Tryptophan & Dopamine

Mrparadise

Senior Member
Messages
100
Likes
147
Dear PR-members

If I understood this the right way, Dr. Ronald Davis' latest research points towards NAD+, tryptophan and dopamine. Did anyone have any success with some supplement and FDA approved drugs which targets those things?
 

nerd

Senior Member
Messages
861
Likes
2,443
What drugs do you have in mind?

For dopamine, Levodopa and Sapropterine can be used.

For the excessive Tryptophan and IDO upregulation, there are two options. First, there are immuno-suppressive vaccinations (e.g. CTB) but they aren't FDA-approved as far as I know (10.3390/vaccines3030703).

Second, there is norepinephrine and IVIG, both of which are approved by the FDA (10.1371/journal.pone.0045491).

But we can think this one step further.

These effects occurred mainly via the β(2)-adrenergic receptor.
Against this receptor type, as we know, often exist antibodies in CFS/ME patients. There is a huge range of β(2)-adrenergic agonists available for this if someone prescribes them to you. The problem with these medications are always the side effects, e.g. Tachycardia, Tremors, Excessive Sweating, Anxiety, Insomnia, Agitation. These are common symptoms in CFS/ME already. You wouldn't want to exacerbate them.

I took low doses of norepinephrine occasionally for some time since I also had allergies with breathing issues. The half dose was sufficient for an effect like others might experience when taking meth, which basically is a large dose of the same medication dissolved from the antihistamine and then sold as a drug. The effect was so severe, I couldn't sleep, my heart was racing, strong heartbeats, hyperactive, euphoria, intense thirst. And the wear-off was the same as well, which means I was completely ruined afterward. Very small doses might be more helpful, but it's impossible to get prescribed separately due to the meth issue. They even took the combo with the third-generation antihistamine off the market here.

The problem is that norepinephrine affects the whole body, while the IDO trap only affects certain cells. You'd need a delivery system to these cells. These technologies exist in cancer research.

Another option that is being discussed is Naltrexone, which can enhance the dopaminergic and norepinephrinergic systems indirectly, which should avoid severe side effects as known from the previous drug candidates (10.1016/0006-8993(85)90794-2).

Regarding NAD+, this is just an indirect effect. The primary problem is the lack of kynurenine availability. Kynurenine has a range of effects parallel to the Niacin pathway, primarily of immunological importance (10.3389/fimmu.2020.00031). By taking NAD+ injections, for example, the positive effects of kynurenine and Niacin are skipped. Kynurenines are opioid receptor agonists (10.3390/biom10020284). So one method to increase their saturation might be taking opioid receptor antagonists such as Naltrexone. But this is just theoretical based on my understanding. We would need to know the receptor affinity of all Kynurenine metabolites. Nevertheless, when Naltrexone interacts with this common receptor, it's possible that there are also other mechanisms of actions within the Kynurenine system.

To compensate for the limited Niacin supply, low doses of Niacin can also help. Independent from that, there still is a lack of oxidation, which reduces ATP replenishment, oxidative phosphorylation, and NAD+ balance. The keto diet can compensate for that to a limited extent. A less potent alternative to the keto diet are BHB supplements. Moreover, chromium picolinate could help normalize the potentially low chromium and picolinate levels.
 
Last edited:

bertiedog

Senior Member
Messages
1,668
Likes
3,212
Location
South East England, UK
Regarding NAD+, this is just an indirect effect
I am having better, more sustained energy with just 150 mg NMN which is linked to NAD+. Been taking it with breakfast for 8 days now and soon noticed a difference. I don't have to rest for very long after preparing breakfast etc before I want to get up and get on with something else which is the opposite of how I am usually am needing to rest until at least 10.30 to get some energy.

It isn't overstimulating to me in the way Carnitine always is or anything else I have tried such as Reishi though I have had a couple of nights when I couldn't get off to sleep without a tiny bit of clonazapan which is probably connected. However I have slept very well and deeply since on it only needing about 6 1/2 hours a night.

The other possible benefit to me is that I haven't had a migraine since taking it (one week) which is unheard of for me. Still get the odd headache first thing but I am pretty sure that is connected to be being low in the steroid overnight and it has cleared after one paracetamol. It's obviously very early days but almost seems to good to be true.

I have also had a virus since Friday but energy held out till yesterday when I had a bad day feeling quite unwell but today has been a lot better which is encouraging. (Also been taking my usual throat sprays and Andrographis 3 times daily).

I bought just 20 capsules from an eBay supplier to try NMN and divided the capsules into 2 putting the other half into an empty capsule giving me 150 mg. I know how sensitive I am to supplements and this has worked out well for me at least at the moment and obviously cuts the cost down too because it can be expensive.

Pam
 

xebex

Senior Member
Messages
674
Likes
1,305
I have just started taking niacin (the flushing type) Niacin is pre the cursor to NAD+. I have noticed an improvement in my muscle fatiguability and PEM. Here’s some interesting links(someone actually already posted them here a couple of weeks ago) about long Covid and some peoples use of niacin in treatment of that. It seems it is a similar theory to the Ron Davis theory.

https://nkalex.medium.com/the-team-...o-seem-to-have-solved-long-covid-5f9852f1101d

 
Last edited:
Messages
1,600
Likes
3,638
Location
United Kingdom
Seems like we could all be one of the many subsets of nutritional blocked pathways currently circulating. Figuring out which one is a real pain.

What's NMN?

Naltrexone seems to have a really low usefulness profile in ME patients though for fatigue. So that casts a bit of doubt on its ability to work around kynurenine? It seems to be amazing for pain and auto immunity tho.

Interesting thread this. So you can buy and inject nad+? Might be an interesting "challenge" to see it be body responds well before taking it more regularly. I'm gradually picking up things that seem to help me although most experiments have been fruitless so far but we keep on going...
 

bertiedog

Senior Member
Messages
1,668
Likes
3,212
Location
South East England, UK
Stands for Nicotinamide Mononucleotide a precursor to NAD+.

I should have said I am heterozygous for both SNPs that are mentioned by Dr Phair as being the most damaging SNPs in his hypothesis which is interesting. There is a post over on the Science4ME forum at the moment and I checked yesterday that I did indeed have this problem. I had sent my 23andme file to Dr Phair who works with Dr David, when he was first requesting ME sufferers on PR to send their data to him several years ago when he first thought there could be a metabolic trap.

Pam
 

bertiedog

Senior Member
Messages
1,668
Likes
3,212
Location
South East England, UK
I have been taking the lower dose of 50-75 mg NMN for the past 14 days with an excellent effect still. I have a lot more sustained energy and only one migraine in 11 days which is unheard of for me. There is a possibility that the nasty daily migraines I started to get at the higher dose might have been caused by Quercertin and not the NMN but anyway I stopped for one day and had a slump in energy so restarted as the much lower dose. as recommended by another expert on it, J E Williams.

Also I have been watching several You Tube videos on NAD+ and its role in ageing, the immune system, DNA repair and lots more. This one is typical of what I mean but I haven't watched all of it yet. I am tempted to buy David Sinclair's book but not sure how technical it is. I find the NAD information absolutely fascinating and it keeps leading me to more and more other interesting topics like what SIRT genes do!


NMN is probably one of the most useful supplement I have taken in 20 years of ME but I should qualify that I am 73 years old and that might be the reason why I get so much benefit from it.

Pam
 

nerd

Senior Member
Messages
861
Likes
2,443
I took low doses of norepinephrine occasionally for some time since I also had allergies with breathing issues. The half dose was sufficient for an effect like others might experience when taking meth, which basically is a large dose of the same medication dissolved from the antihistamine and then sold as a drug. The effect was so severe, I couldn't sleep, my heart was racing, strong heartbeats, hyperactive, euphoria, intense thirst. And the wear-off was the same as well, which means I was completely ruined afterward. Very small doses might be more helpful, but it's impossible to get prescribed separately due to the meth issue. They even took the combo with the third-generation antihistamine off the market here.
I just noticed a mistake. I didn't take "norepinephrine", a natural hormone. I took "pseudoephedrine". It targets alpha-adrenergic receptors more than beta-adrenergic ones.
 

pattismith

Senior Member
Messages
3,425
Likes
6,700
Dear PR-members

If I understood this the right way, Dr. Ronald Davis' latest research points towards NAD+, tryptophan and dopamine. Did anyone have any success with some supplement and FDA approved drugs which targets those things?
Many drugs targeting dopamine have been use with some improvement in fibro, restless legs and ME/CFS , even though they are not approved for our diseases.

.. Some antipsychotics used for Schizophrenia (neuroleptics)
Antipsychotic - Wikipedia

.. Dopaminergic drugs for Parkinsons (Pramipexole...)
Parkinson's disease - Wikipedia

.. Dopaminergic drugs used in ADHD and Narcolepsy (Modafinil, Methylphenidate...)
Dopamine reuptake inhibitor - Wikipedia


you will find threads in this forum discussing some experience members had with these drugs.
Many of these drugs are sensitive ones, they can cause tolerance, addiction and side effects and must be use with caution.
People who used it usually failed with many other drugs before, including SSRI or other.

NAD+ is useful for many people.
It can help you if you are short in it (usually your blood lactates raise when you lack NAD+).

If you need it you will find a quick positive effect, so it is worth a try

1626025862788.png


Personnally I currently can't fonction if I don't take Methyphenidate, and I also take some NAD+, but didn't try tryptophan