Noradrenaline-deficient type of CFS

[cfsJapan]

I have been diagnosed with CFS＋ADHD, and when I take medications that increase dopamine, even the smallest amount makes me manic, and my impulsivity and stereotyped behavior worsen.

However, when I take medications that increase norepinephrine, all of my symptoms improve immediately.

(Strangely enough, I also suffer from chronic fatigue syndrome, and when I take medications that increase norepinephrine, not only my CFS＋ADHD but also my chronic fatigue syndrome improves.)

In this case, is it possible that my ability to convert dopamine to noradrenaline is low?

Also, is there a way to increase noradrenaline other than simple reuptake inhibition? (I'm thinking of taking noradrenaline precursors and SaMe, but do you think that's a foolish idea?)

The medication that works dramatically for my ADHD is Nortriptyline. Then there's Imipramine. But both of them significantly extend my QT at around 5-10mg, so I can't continue using them.

Also, Cymbalta was great for my CFS＋ADHD for the first two months, but now I only feel the effect of serotonin and I have no motivation at all.

Even more strangely, Atomoxetine had no effect at all. I have a tendency to have difficulty metabolizing drugs that involve cyp2d6. (So I'm considering a noradrenaline reuptake inhibitor other than Atomoxetine, but Qelbree and Reboxetine are not sold in Japan.)

And even more strangely, Lamotrigine and Clonazepam improve my CFS＋ADHD (I usually don't have any anxiety symptoms, and people point out that they might be working on anxiety, but that's not the case at all.)

I'm happy to have some hints for improvement, even if it's just a partial answer.

When I take Nortriptyline, my noradrenaline level increases, my visual function improves, communication becomes smoother, and I can do what I need to do calmly. It's a real shame that I could have continued if I didn't have heart problems.

 

[Violeta]

Mechanisms of Ascorbic Acid Stimulation of Norepinephrine Synthesis in Neuronal Cells​

https://pmc.ncbi.nlm.nih.gov/articl...,norepinephrine synthesis in cultured neurons.

Interesting, I didn't know about this.

 

[bad1080]

Mechanisms of Ascorbic Acid Stimulation of Norepinephrine Synthesis in Neuronal Cells​

https://pmc.ncbi.nlm.nih.gov/articles/PMC3449284/#:~:text=Ascorbic acid is well known,norepinephrine synthesis in cultured neurons.

Interesting, I didn't know about this.

this might explain the good day i had after starting vit.c, it felt like oxygen was able to reach my cells again. but as with so many supplements it was a one-off never to be replicated again.

 

[linusbert]

eggs, methylation support, vitamin c, b5, sodium. b6!
any methylation support will make you go insane especially b6. you need to go slow , like 1 b6 supplement PER WEEK, not day. and then do 2 days a week, slowly go up.

your body is adapted to low levels of neurotransmitters, that means any increase will be like poisoning. until the body slowly downregulates receptors and becomes more tolerant again. that becoming manic seams to be such a reaction.

 

[linusbert]

Mechanisms of Ascorbic Acid Stimulation of Norepinephrine Synthesis in Neuronal Cells​

https://pmc.ncbi.nlm.nih.gov/articles/PMC3449284/#:~:text=Ascorbic acid is well known,norepinephrine synthesis in cultured neurons.

Interesting, I didn't know about this.

that actually explains why i do have more energy and less crashing on vitamin c!
also my post orgasmic pem will be prevented.

also vitamin C is very much required for endogen creatine and carnitine production.
ai: "A deficiency in vitamin C can impair carnitine production, potentially leading to fatigue and muscle weakness."

 

[Violeta]

There are a lot of studies out there about this!

https://pmc.ncbi.nlm.nih.gov/articles/PMC3527656/

https://www.sciencedirect.com/science/article/abs/pii/S0006291X12015641

Wow, the ascorbate also maintains BH4.
These results suggest that expected physiologic neuronal ascorbate concentrations enhance norepinephrine synthesis both by maintaining tetrahydrobiopterin and increasing tyrosine hydroxylase expression.

https://www.sciencedirect.com/science/article/abs/pii/S0361923012002092

These results show that ascorbate promptly enhances norepinephrine synthesis from dopamine by neuronal cells that it does so at physiologic intracellular concentrations in accord with the kinetics of DβH, and that it both protects cells from superoxide and by providing electrons to DβH.

 

[Violeta]

There are a lot of studies out there about this!

https://pmc.ncbi.nlm.nih.gov/articles/PMC3527656/

https://www.sciencedirect.com/science/article/abs/pii/S0006291X12015641

Wow, the ascorbate also maintains BH4.
These results suggest that expected physiologic neuronal ascorbate concentrations enhance norepinephrine synthesis both by maintaining tetrahydrobiopterin and increasing tyrosine hydroxylase expression.

https://www.sciencedirect.com/science/article/abs/pii/S0361923012002092

These results show that ascorbate promptly enhances norepinephrine synthesis from dopamine by neuronal cells that it does so at physiologic intracellular concentrations in accord with the kinetics of DβH, and that it both protects cells from superoxide and by providing electrons to DβH.

Looks like oxygen is needed, too.

Dopamine is converted into norepinephrine by the enzyme dopamine β-hydroxylase (DBH), with O2 and L-ascorbic acid as cofactors.

Under hypoxic conditions, the conversion of dopamine to norepinephrine is typically decreased because the enzyme responsible for this conversion, dopamine beta-hydroxylase (DBH), requires oxygen as a cofactor, meaning low oxygen levels will significantly inhibit its activity and therefore reduce the production of norepinephrine from dopamine;

 

[Violeta]

I saw a list of other things that increase norepinephrine. Quercetin was one of them.

Quercetin is a flavonoid found in fruits, vegetables, and grains that may increase norepinephrine levels in the plasma. Quercetin may also inhibit the enzyme that breaks down norepinephrine, monoamine oxidase (MAO).

How quercetin affects norepinephrine

• Inhibits MAO: Quercetin may inhibit MAO, which breaks down norepinephrine and other neurotransmitters that affect mood.
  
  
• Increases plasma norepinephrine: Quercetin supplements may increase norepinephrine levels in the plasma.
  
  
• Upregulates β-adrenergic receptors: Quercetin may upregulate the mRNA expression of β-adrenergic receptors.
  
  
• Activates AMPK: Quercetin may activate AMP-activated protein kinase (AMPK), which modulates inflammation and oxidative stress.
  

 

[bad1080]

would sodium ascorbate be a sufficient substitute for these reactions to take place?
https://en.wikipedia.org/wiki/Sodium_ascorbate

i have to be careful with acidity due to my gastritis

 

[Violeta]

would sodium ascorbate be a sufficient substitute for these reactions to take place?
https://en.wikipedia.org/wiki/Sodium_ascorbate

i have to be careful with acidity due to my gastritis

I don't know, I hope so. I have to be careful, too. I can take ascorbic acid with foods but I take calcium ascorbate when I want to take some without food. This seems to be working.

 

[Violeta]

These data demonstrate that a bout of thiamine deficiency can produce persistent deficits in brain norepinephrine and concomitant decrements in behavioral measures of learning and memory.

Thiamine deficiency depletes cortical norepinephrine and impairs learning processes in the rat​

https://pubmed.ncbi.nlm.nih.gov/4075172/

 

[Violeta]

Norepinephrine (NE) is an important neurotransmitter in the central nervous system. NE is released from locus coeruleus neurons and is involved in a variety of physiological and pathological processes. Neuroinflammation is a common manifestation of many kinds of neurological diseases. The activation of microglia directly affects the status of neuroinflammation. Several kinds of adrenergic receptors, which anchor on microglia and can be regulated by NE, affect the activation of microglia and neuroinflammation. NE influences chronic pain, anxiety, and depression by regulating the activation of microglia

Effects of norepinephrine on microglial neuroinflammation and neuropathic pain​

https://onlinelibrary.wiley.com/doi...ortant,regulating the activation of microglia.

 

[Violeta]

If your glymphatics aren't draining, norepinephrine deficiency could be the reason.

Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep​

https://www.cell.com/cell/abstract/...m/retrieve/pii/S0092867424013436?showall=true

 

[Violeta]

would sodium ascorbate be a sufficient substitute for these reactions to take place?
https://en.wikipedia.org/wiki/Sodium_ascorbate

i have to be careful with acidity due to my gastritis

I started taking ascorbyl palmitate, also known as ester c, and it's not so hard on the stomach.

I started taking it for a different reason, but just that reason alone is enough to switch to it.

This is a study related to why I started taking it. If n-linked glycosylation is messed up, one might end up having a vitamin c deficiency because of not being able to get it into the cell.
This is a topic I got interested in because of research by mariovitali.

Ascorbyl palmitate is absorbed through the cell membrane, so bypasses the vitamin c transporter issue.

There are supplements you can take to correct glycosylation issue, too, such as taurine and choline.

N-glycosylation is required for Na+-dependent vitamin C transporter functionality​

https://pmc.ncbi.nlm.nih.gov/articles/PMC2528843/

 

[bad1080]

I started taking ascorbyl palmitate,

thank you! is that similar to/the same as liposomal vit.c? i had that a while ago (as a thick liquid iirc) but it didn't do anything for me.

 

[linusbert]

This is a study related to why I started taking it. If n-linked glycosylation is messed up, one might end up having a vitamin c deficiency because of not being able to get it into the cell.

good point, i just recalled that vitamin c is competing with glucose.

Ascorbyl palmitate is absorbed through the cell membrane, so bypasses the vitamin c transporter issue.

is it based on palm oil.. i fear the name.

thank you! is that similar to/the same as liposomal vit.c? i had that a while ago (as a thick liquid iirc) but it didn't do anything for me.

to my understanding its not related. liposomal is transportation of something via micro fat bubbles as encapsulation. could be anything. its like a shuttle bringing stuff into the cell. what the stuff is is flexible.

 

[Violeta]

thank you! is that similar to/the same as liposomal vit.c? i had that a while ago (as a thick liquid iirc) but it didn't do anything for me.

No, ascorbyl palmitate is different from liposomal vit c. I can't take liposomal products. That thick liquid that doesn't dissolve in water causes me issues really fast.

 

[lyran]

I noticed a few years ago when I take l-tyrosine alone, it takes around 6 hours to get the "brain boost" effect but if I take it with vitamin c, it only takes 1-2 hours. Just saying as it is related to this discussion (vitamin c - noradrenaline connection).

 

[Violeta]

I noticed a few years ago when I take l-tyrosine alone, it takes around 6 hours to get the "brain boost" effect but if I take it with vitamin c, it only takes 1-2 hours. Just saying as it is related to this discussion (vitamin c - noradrenaline connection).

Good point, I will start taking tyrosine with the C.