7 Day NAD+ Infusions (Severe ME/CFS Recovery, Neurological / Mitochondrial / Genetic Repair) + POLL

[Learner1]

What is NMN?

As the article states, nicotinamide mononucleotide, a precursor of NAD+.

 

[triffid113]

I am going to get a homocysteine test but it will only inform me how much harder I have to try. Since I didn't get this test b4 I started taking niacinamide (and my skin seems 2 really need it at 62). However I have had a bad reaction to bug bites and had to ramp up b vitamins, so... not sure what I'd be testing right now. I ran out of TMG today but have plenty of choline, which I read can be converted to TMG. I ordered a multiple with active B's (I had one before but it was a 6/day and I only took 2/day. This one is 2/day). So... too bad I didnt get a revent homocysteine b4 I started taking niacinamide. I dont really get why it would affect methylation unless b2 is involved on methylation? I kniw the Kreb/TCA cycle usrs both nad and fad (b2) so I would think supplementing high b3 would deplete b2. So... logically I would need more b3. Guess I'll look into that. At this point I can only go forward. Anyway, I want 2 thank u for sharing all your knowledge!

 

[triffid113]

oops, Typo! Logically extra b3 woyld require extra b2, s far as i can see.

 

[Learner1]

B2 is used to support the MTHFR reaction, so yes, it is involved with methylation.

Taking B3 will increase the need for folate, B6 and B12. And probably B2.

 

[mitoMAN]

Resume:
NAD+: I did 9 days of NAD+ 300-600mg total of 3600mg over the 9 days and stopped yesterday
NADH: 16 days of 150-400mg NADH total of 5000mg ongoing (but went out of supply today)

I can say that the effect built up every day.
While NAD+ hat consistent negative reaction after administration - I took it before going to sleep and had to sleep 12+ hours then. This is why I tried to stop it now and see there: I need to sleep 7-8 hours.

The NADH gives consinstent energy after injection of each 100mg set. I ran out of NADH today but am still very energetic and mentally fit.


Was visiting my brother today and he asked what I was doing because he hasnt seen me like this for over a year.
So it indeed seems to be not only a subjective improvement but also recognizeable by persons that havent seen me for awhile (havnt seen him for 2 months)

I just re-ordered 50 000mg NAD+ and 25 000mg NADH but should have probably switched the numbers around. More NADH less NAD+. Did the order before I came to that conclusion. DOH.


I am going to try NMN injections low dose next week and might want to try NR injections in a month.

Interestingly I have zero improvement from oral NMN or NADH. Zero. Wondering if this could be related to my gut problems and leaky gut (currently being treated for it)

 

[Learner1]

Thanks for the update. Just curious, where does one get injectable NMN?

And were you taking the NMN and NADH through your digestive system or doing it sublingually? It makes a big difference. Through the digestive system may not work because things get broken down before they get to know where they need to go. Sublingually should get straight into your bloodstream. If that doesn't work, you might look into genetic variations. For me I've got two genetic variations that prevent me from using the NR. I don't think they're too uncommon, so I expect others would have the same issue.

The only other comment I can make is that is an awful lot of NAD. I'm wondering why you're not recycling between NAD and NADH. Seems like there's some sort of leak somewhere in the process, which is why you're so needy. Or at least that's my guess. Or... What is the explanation? I guess another place to look could be the quality of your mitochondrial membranes, and if peroxynitrites had damaged them, and you're short of phospholipids to repair them that would make them leaky and make ATP production less efficient.

Or, maybe it's just the flaw with complex 5 as a few of the Australian researchers have found. I am not convinced that that's my problem, but it could indeed be yours. The devil is in the details, isn't it?

I know that too much NAD gives me horrendous symptoms, makes me jittery, makes my intestines want to dump, and gives me excruciating muscle pains in my forearms and legs very fast. So, I've learned a little bit on a regular basis seems to work for me.

 

[mitoMAN]

Thanks for the update. Just curious, where does one get injectable NMN?

I am buying raw powder straight from wholesale manufacturers in China, a friend did a HPLC check on the NADH and is it was pure without additives and impurities, I figured their NAD+ and NMN and NR is probably safe as well.
As you probably know, 90% of the NMN is produced there for the global market.
China isnt always a bad thing. But you have to be careful - especially if you dont know what you are doing.

I am doing my own bacterial filtering and constitution with freezing which I wouldnt advise to anyone else.

And were you taking the NMN and NADH through your digestive system or doing it sublingually? It makes a big difference. Through the digestive system may not work because things get broken down before they get to know where they need to go. Sublingually should get straight into your bloodstream

I was taking the NADH sublingually from Birkmayr (the guy that did most Parkinson Studies on it and sells it)
The NMN I did two months of sublingual and the remaining months orally. Honestly didnt notice ANY effect from any of the sublingual intakes. Which makes me wonder if my serum peaks need to be much higher and thus the injectible NADH is doing wonders contrary to even 200mg sublingual NADH (recommended dosage is 20-40mg!)

If that doesn't work, you might look into genetic variations. For me I've got two genetic variations that prevent me from using the NR. I don't think they're too uncommon, so I expect others would have the same issue.

I have a Whole Genome Sequencing I can browse on PROM or GenVue so I would be highly interested to get a reference for possible NR or NMN variations! Those should be listed in my clinVar but probably not linked to NR or NMN so I havnt really looked into them yet.

The only other comment I can make is that is an awful lot of NAD.

To be honest, I started the NAD+ in regards to the "proposed" 7 days I.V that many clinics advertise but which are probably a total waste. So I slowed down to 300mg per day and decided to finally pause it and see if I will notice any ongoing benefits.

It was pure self-experimentation which again, I dont recommend to anyone else.

The only other comment I can make is that is an awful lot of NAD. I'm wondering why you're not recycling between NAD and NADH. Seems like there's some sort of leak somewhere in the process, which is why you're so needy. Or at least that's my guess. Or...

Indeed it is an aweful lot. Especially the NADH. Usually I.V.s are done with 20-50mg NADH! I am starting to feel very good effect from 300mg on. Which also made me wonder if my Complex I may be impaired already and I could possibly have a deficit in NADH contrary to most having a deficit in NAD+?

There must be a reason why I react VERY good to NADH and kind of non existant to NAD+.
Luckily I have been blessed with almost never encountering side effects from medication. They either just dont work but never leave me with heavy sides. So even 300mg NAD+ makes me dizzy and tired, but thats it.

What is the explanation? I guess another place to look could be the quality of your mitochondrial membranes, and if peroxynitrites had damaged them, and you're short of phospholipids to repair them that would make them leaky and make ATP production less efficient.

Indeed I think my mitochondrial membrane is suffering from the heavy oxidative stress and producing toxic leakage. My intracellular ATP measured very low as well even after 5 months of all possible NAD+ oral boosters,

Thats why I will be starting SS-31 pretty soon and report back - its one of the strongest mitochondrial repairing peptides and should stabilize the membrane and scavange oxidative stress and ROS more effectively than any other supplement.

I m just waiting for a 3rd Party lab test of my SS-31 sample to confirm my custom synthed product is legit and not harmful.

 

[Learner1]

Er, what are your phospholipids like? Phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidyl ethanolamine? I'll need to be sufficient to make/repair mitochondrial membranes.

And peroxynitrite status? Peroxynitrites will shred mitochondrial membranes and impair complex 1, making for very inefficient ATP production. Perhaps looking into this area, and having sufficient folate, B12, C, and BH4 would reverse the peroxynitrite production and replenishing with phospholipids as Garth Nicholson and Patricia Kane have suggested might improve the quality of your mitochondrial membranes and make your ATP production more efficient, resulting in less need for NADH? I've done a lot of work in this area, and my energy has improved dramatically. Perhaps that's why I need a lot less NAD than you do?

NMRK1 and 2 SNPs seem to interfere with use if BR and d-ribose. Not sure what the other genes might be affecting NAD production, but they would support one of these four different methods of creating NAD+.

SS-31 is a mitochondrial antioxidant. Wonder if it would attack the superoxide production which is combining with nitric oxide, which forms the peroxynitrites instantaneously when superoxide radicals are produced? I know SS-31 was the only thing that passed the nanoneedle test, but what exactly is it doing? What is the mechanism? And is there some other combination of antioxidants that would work? The last three articles attached below discuss oxidative and nitrosative stress and mitochondria and use of various substances to tackle it.

 

[Learner1]

It's interesting to notice that NAD+ which is also a mitochondrial activator and an akt/mTor inhibitor (via sirt1 activation) can have both pro or anti cancer activity, depending of the cell or situation.

NAD+ given at high dose can also be hepatotoxic.

I quoted this from another thread as it is pertinent to this discussion. Thank you for finding the article, it makes very good points. @Hopeful2021 @mitoMAN

This is why I have an advocating for only taking as much as one needs, and not taking extraordinarily high doses which could backfire.

 

[mitoMAN]

Er, what are your phospholipids like? Phosphatidylcholine, phosphatidylserine, phosphatidylinositol, and phosphatidyl ethanolamine? I'll need to be sufficient to make/repair mitochondrial membranes.

And peroxynitrite status? Peroxynitrites will shred mitochondrial membranes and impair complex 1, making for very inefficient ATP production. Perhaps looking into this area, and having sufficient folate, B12, C, and BH4 would reverse the peroxynitrite production and replenishing with phospholipids as Garth Nicholson and Patricia Kane have suggested might improve the quality of your mitochondrial membranes and make your ATP production more efficient, resulting in less need for NADH? I've done a lot of work in this area, and my energy has improved dramatically. Perhaps that's why I need a lot less NAD than you do?

My German labs dont offer subgroups of phospholipids.

The tests I did were limited to

• Malondialdehyd-modified LDL/MDA-LDL
• Nitrotyrosin
• Total Antioxidative Capacity(TAC)
• Glutathionperoxidase (GPx)
• Glutathion intracellular (GSH)
• Vitamin C
• Vitamin E
• Selen
• Zinc
• All other possible minerals and vitamins ofc. No defecit was found
• Homocystein
• CoQ10
• intracellular ATP

I am taking about all possible supplements, including high dose B12 injections of Methyl and Adenosylcobalamin, 5-MTHF etc etc. These didnt bring any subjective improvement.

I have to say that I blieve that the NAD+ didnt bring any short term improvement as well.
It was purely NADH that brings immediate improvement - within 10-30 minutes for several hours per day!

The idea behind SS-31 is to improve my mitochondrial membrane potential and antioxidative capacity by ALOT. No other substance has been shown to be as effective as SS-31. So thats worth a shot.

Also I havent tried C-60 yet. Would you recommend this?
I currently try 400mg Ubiquinol CoQ10 instead of 2g Ubiquinon CoQ10 and see if that helps.
As my CoQ10 level were rather low even tho I supplemented Ubiquinon for 5 months.

SS-31 is a mitochondrial antioxidant. Wonder if it would attack the superoxide production which is combining with nitric oxide, which forms the peroxynitrites instantaneously when superoxide radicals are produced? I know SS-31 was the only thing that passed the nanoneedle test, but what exactly is it doing? What is the mechanism? And is there some other combination of antioxidants that would work? The last three articles attached below discuss oxidative and nitrosative stress and mitochondria and use of various substances to tackle it.

Studies are missing on combining SS-31 with other antioxidants. However according to studies, a higher dose of SS-31 will make up for any other oral supplementation regarding membrane potential, ROS Scavanaging, intracellular Glutathione, antioxidative capacity etc.
It has shown to completly restore dysfunctional mitochondria back to Healthy Controls.
Which is extremly promising. And it even were human trials. Not just some mice trials.


I will have a look in my WGS to search for possible NR or NMN metabolism dysfunctions. I havent tested NR yet. But will hopefully find out about injectible NMN soon. I am also planning to try injectible NR if NMN doesnt work.

 

[mitoMAN]

I quoted this from another thread as it is pertinent to this discussion. Thank you for finding the article, it makes very good points. @Hopeful2021 @mitoMAN

This is why I have an advocating for only taking as much as one needs, and not taking extraordinarily high doses which could backfire.

Indeed this is what I have been reading as well. It surely is a double edged sword for different cancer cells and as you said, dosing high NAD+ especially if one DOESNT NOTICE IMPROVEMENTS is possibly dangerous.

 

[Learner1]

Even if one thinks it's working, it can be potentially dangerous. I developed stage three cancer doing everything right, and the type of cancer it was, it was growing likely for a few years, before it suddenly became obvious.

 

[mitoMAN]

This is very correct. NAD+ supplementation and precursors are still very poorly studied regarding long term side effects

 

[Learner1]

My German labs dont offer subgroups of phospholipids.

The tests I did were limited to

• Malondialdehyd-modified LDL/MDA-LDL
• Nitrotyrosin
• Total Antioxidative Capacity(TAC)
• Glutathionperoxidase (GPx)
• Glutathion intracellular (GSH)
• Vitamin C
• Vitamin E
• Selen
• Zinc
• All other possible minerals and vitamins ofc. No defecit was found
• Homocystein
• CoQ10
• intracellular ATP

I am taking about all possible supplements, including high dose B12 injections of Methyl and Adenosylcobalamin, 5-MTHF etc etc. These didnt bring any subjective improvement.

I have to say that I blieve that the NAD+ didnt bring any short term improvement as well.
It was purely NADH that brings immediate improvement - within 10-30 minutes for several hours per day!

The idea behind SS-31 is to improve my mitochondrial membrane potential and antioxidative capacity by ALOT. No other substance has been shown to be as effective as SS-31. So thats worth a shot.

Also I havent tried C-60 yet. Would you recommend this?
I currently try 400mg Ubiquinol CoQ10 instead of 2g Ubiquinon CoQ10 and see if that helps.
As my CoQ10 level were rather low even tho I supplemented Ubiquinon for 5 months.


Studies are missing on combining SS-31 with other antioxidants. However according to studies, a higher dose of SS-31 will make up for any other oral supplementation regarding membrane potential, ROS Scavanaging, intracellular Glutathione, antioxidative capacity etc.
It has shown to completly restore dysfunctional mitochondria back to Healthy Controls.
Which is extremly promising. And it even were human trials. Not just some mice trials.


I will have a look in my WGS to search for possible NR or NMN metabolism dysfunctions. I havent tested NR yet. But will hopefully find out about injectible NMN soon. I am also planning to try injectible NR if NMN doesnt work.

I don't know C60. What is it, please?

I take 100mg Thorne Q Best and 10mg MitoQ. That's not much compared to some patients around here, but my issues don't seem to be in that area. MitoQ, which can be bought over the internet from New Zealand it's supposed to be better for getting into the mitochondria, otherwise ubiquinol of some sort is best.

I look back at your labs that you shared, and your nitrotyrosine was at the top of the range, which does indicate that you have problems with peroxynitrites. Peroxynitrites shred mitochondrial membranes and impair complex 1. This leads to inefficient or impaired ATP production, and not dealing with them will cause this sort of problem to snowball and become a lot worse over time. This alone could be why you are needing so much NAD if you're fighting this problem. It would be helpful to know what your phospholipids are doing, but you might look into a product like NT Factor, formulated by Garth Nicholson, which has all of the phospholipids needed for the membranes and the correct ratios to one another. Or you could do IVs of phosphatidylcholine. I believe Lipostabil is a variety that's been available in Switzerland.

Another possibility might be that you have arsenic toxicity. Arsenic can impair ATP production. Another explanation could be huge oxidative stress (also indicated by the nitrotyrosine, as peroxy nitrites are formed when superoxide radicals made by the mitochondria react with nitric oxide to form them instantaneously). Increasing the whole network of antioxidants would help, but getting to the bottom of where the superoxide radicals are being produced in such a great quantity and shutting that down to a dull roar would be helpful.

The other thing you're lab suggest, if I'm not mistaken, is that you have some sort of infection going on. Infections like chlamydia pneumonia impact energy production, and many others do as well. So working on that would likely be helpful with your doctors.

 

[mitoMAN]

I just checked my Whole Genome and found some interesting data.
This could explain the theory on why my mitochondrial membrane potential is so damaged and NO is having a huge impact on it as well as regular oxidative stress.

Indeed this might be a reason why NADH revives my Complex I ?


Homozygote Risk Allels in

TNF-A G-308A [rs1800629] GG https://www.snpedia.com/index.php/Rs1800629 (30% Frequency so less important)

IL1RA T2010C [rs419598] CC https://www.snpedia.com/index.php/rs419598

IL1B [rs1143642] CC https://www.snpedia.com/index.php/rs1143642

IL1RL1 [rs11685480] AA https://www.snpedia.com/index.php/rs11685480

IL1RN [rs9005] AA https://www.snpedia.com/index.php/Rs9005

SOD1 [rs1041740] TT https://www.snpedia.com/index.php/Rs1041740


IL-1B has been shown to have huge impact on NO formation.
I have extremly high IL-1B blood levels possibly also due genetic polymorphism.


Martin Pall - NO (Nitric Oxide) in CFS
https://me-pedia.org/wiki/Nitric_oxide_hypothesis

„I propose here a novel hypothesis of CFS in which either viral or bacterial infection induces one or more cytokines, IL-1beta IL-6, TNF-alpha and IFN-gamma.
These induce nitric oxide synthase (iNOS), leading to increased nitric oxide levels. Nitric oxide, in turn, reacts with superoxide radicals to generate the potent oxidant peroxynitrite. „



-> Possible therapy with IL-1 Receptor Antagonist OR Celecoxib.


CELECOXIB INHIBITS IL-1 -INDUCED PRODUCTION OF MATRIX METALLOPROTEINASES AND NITRIC OXIDE
(PDF im Anhang)

„Nitric Oxide mediates infection, inflammation, and immunologic reactions. NO is generated by nitric oxide synthase (NOS).
Proinflammatory cytokines such as interleukin-1 (IL-1 ) up-regulate inducible form of NOS (iNOS) as well as COX-2 and MMPs.
NO has also been shown to activate COX- 2 (4) and MMPs (5).“

„IL-1 at 2 ng/ml enhanced the production of MMP-1 and MMP-3 in OA chondrocytes.
When chondrocytes were coincubated with celecoxib in the presence of IL-1 , the COX-2 inhibitor suppressed the IL-1 - induced MMP production in a dose dependent manner.
Celecoxib reduced IL-1 -stimulated NO levels in a dose dependent manner. The inhibitor at 100 nM decreased IL-1 -induced NO by approximately 70% (6.222 5.141 nmol/g, P<0.0001).
Treatment with 100 nM celecoxib resulted in a significant inhibition of MMP-1 (P=0.0008) and MMP-3 (P=0.0008).“




SOD1 rs1041740 T:T
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068777/
Oxidative stress is the excessive accumulation of reactive oxygen species (ROS) relative to antioxidant activity and is a major cause of cardiovascular disease [6,7].
Superoxide dismutase-1 (SOD1) is an antioxidant protein that plays a pivotal role in reducing ROS by catalysing superoxide into oxygen and hydrogen peroxide [8].
Previous reports demonstrated that some SOD1 SNPs are associated with the development of cardiovascular disease [9,10,11]

Multivariate Cox proportional hazard regression analysis revealed that the homozygous T-allele of rs1041740 was associated with all-cause and cardiovascular deaths after adjusting for confounding factors.
The net reclassification index was significantly improved by adding rs1041740 as a cardiovascular risk factor.



General SOD1 and rs1041740 information
https://www.geneticlifehacks.com/sod1-gene-polymorphisms/

 

[mitoMAN]

It would be helpful to know what your phospholipids are doing, but you might look into a product like NT Factor, formulated by Garth Nicholson, which has all of the phospholipids needed for the membranes and the correct ratios to one another. Or you could do IVs of phosphatidylcholine. I believe Lipostabil is a variety that's been available in Switzerland.

Thank you and very interesting - I just asked my friend who is an ongoing doctor and helps me with the NADH injections and filtering etc.

He is doing:
Micellized Pure PC - Phosphatidylcholine
https://www.lifeextensioneurope.co....5Sf2bmDR36xPys-keJN74zUH0PNCZRiBoCecIQAvD_BwE



I might try the NT factor - it seems to have a huge variety of Phoshoplipids and not just phosphatidylcholine?
Also would you prefer a liposomal product over regular powder (NT)?

 

[Learner1]

NT Factor has really made a difference, at 2-3 scoops a day. It gas the correct ratio of each of the phospholipids found in our cells. Better than just phosphatidyl choline, even liposomal. The lipids in NT Factor seem to get where they need to go.

 

[Learner1]

This paper was just published last week:

https://advances.sciencemag.org/content/early/2020/09/08/sciadv.abe5310

 

[junkcrap50]

Found this fact interesting. Lactateyruvate ratio reflects NADH:NAD+ ratio.

The blood lactate-to-pyruvate (L)1 molar ratio reflects the equilibrium between product and substrate of the reaction catalyzed by lactate dehydrogenase. The L ratio is correlated with the cytoplasmic NADH:NAD+ ratio and is used as a surrogate measure of the cytosolic oxido-reduction state (1). When cellular respiration is impaired, as in hypoxia, pyruvate oxidation is reduced, resulting in lactic acidosis. In such situations, reduced forms of oxido-reduction coenzymes (NADH, FADH2) predominate and L ratio is increased.
Source: https://academic.oup.com/clinchem/article/53/5/916/5627488

 

[Learner1]

Very interesting. Wonder how if correlated to this, which says high lactate can be from thiamine deficiency, among other things...