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

[junkcrap50]

I didn't even know there is direct ATP supplementation... does that help at all? Or just for the transport

Yes, here is a thread that's recently been discussed: https://forums.phoenixrising.me/threads/atp-working-well-for-me.81086/ One person has had success with it. It may also be called "adenosine" as it's drug name. I've only heard of it here on phoenix rising, when it's used in combination with glutathione shots to help transport it into cells. But some people using glutathione + ATP shots said it was like rocket fuel. Also one person I remember was considering getting infusions of it (as ADP, I think) from their doctor. It's used only in irregular heart beats. I've never researched it extensively, as its likely impossible to get. I do wonder why it its tried more since doctors prescribe it for glutathione shots.

If NAD+ didn't help. You should try NADH

Good idea. I tried the NADH sublingual tabs a long time ago. But never over a long period of time and likely low doses. How do you take your NADH? What doses did you see benefits at?

1500mg NAD+ costs about 20USD max in bulk orders from licensed labs (as a doctor)

as private person you can source from China and have it 3rd party lab tested yourself in the USA.
1500mg NAD+ for about 10USD and 250USD lab testing once for the whole supply

Yes. The drug itself is very cheap. I've posted the prices of it from US compounding pharmacies here on phoenix rising. I believe it's $75 for 500mg. Or was. Can you PM me the source for $20 NAD+? I wouldn't trust sourcing it from labs from China. I know you can 3rd party test it and all, but that's just out of my comfort zone. Especially when administrating it via IV.

 

[Hopeful2021]

I did not see any benefit or improvement from doing IV NAD+. But I still think it was worth doing because it does help on a cellular and DNA level. I sometimes wonder if perhaps my 2 sets of 10 days of infusions were just not enough. That my NAD+ levels were so low that I just needed to do more infusions. But from the anecdotes and protocols online, most people see a response very quickly. There may be a proglem with NAD+ recycling as it does get consumed quickly and needs to be recycled. Perhaps that is why it didn't work. But I didn't really investigate NAD+ recycling. I'm taking oral NAD+ and NMN daily now.

@Learner1 also responded well to NAD+ infusions. You can ask her how quickly her response was.



Many months? How many infusions did it take? How many infusions per week (per month) were you doing? Interesting that it took so long for you. How did you know to keep going? Many protocols keep it to 10 days (10 infusions). Do you feel that the glutathione infusions are essential following NAD+ infusions? To get the benefits of NAD+?

I did months of NAD IV.
I did 1, then 2 IVs a week.
I wasn't strong enough in the beginning to
do many times a week. And I wasn't strong enough to travel to a clinic to do the 10 day protocol.
If i knew now that indeed NAD IV worked so well, i would have tried when i got strong to get to one.

Yes, the glutathione after was a recent addition. It is amazing and gave my already good progress a huge bonus.
Glutathione is something ppl have varying tolerances for. Same with NAD. Sometimes I am so ill during it... but I persist and then almost 2 hours later feel really super, am very strong, great brain/vision/muscles mind everything. Sometimes IV is no big deal, maybe great after effects , maybe just normal good benefits.

The subQ shots have really a wide range of good to not so fun effects. It's my maintenance program to keep me from dipping so low between IVs.

My NAD IV dose now also varies on what i think i can handle, time for drip, if I'll be getting another that week, if I was in a crash, etc. 300mg to 1,000mg.

 

[Hopeful2021]

I did not see any benefit or improvement from doing IV NAD+. But I still think it was worth doing because it does help on a cellular and DNA level. I sometimes wonder if perhaps my 2 sets of 10 days of infusions were just not enough. That my NAD+ levels were so low that I just needed to do more infusions. But from the anecdotes and protocols online, most people see a response very quickly. There may be a proglem with NAD+ recycling as it does get consumed quickly and needs to be recycled. Perhaps that is why it didn't work. But I didn't really investigate NAD+ recycling. I'm taking oral NAD+ and NMN daily now.

@Learner1 also responded well to NAD+ infusions. You can ask her how quickly her response was.



Many months? How many infusions did it take? How many infusions per week (per month) were you doing? Interesting that it took so long for you. How did you know to keep going? Many protocols keep it to 10 days (10 infusions). Do you feel that the glutathione infusions are essential following NAD+ infusions? To get the benefits of NAD+?

That's interesting you did 2 rounds of ten days. Wow.
Do you know if you did Fresh from a vial NAD or the powder mix kind?

I do fresh from the vial and liked one compound pharmacy more than another. Also, my doc and I discovered that i do better with co-nutrients in the bag. I get amino acid profile to know i have the methyl donors. Sometimes we add more aminos though if I am getting too nauseous.
I'm also in ketosis and my doctor has observed that his less inflammatory patients do better on NAD. His carb and high carb ones usually can't take the feeling and don't get more IVs.

Almost all of my IVs have been while I'm fasting. Later in the last months, occasionally I will snack on meat or cheese the last 1.5 hour or so. After the majority of the 1,000mg IVs that were NOT followed by glutathione, I would eat huge amounts of meat. (I'm mainly carnivore). My hunger would also equate in lots of energy.... meaning long walks or home projects.

I also do hours of neuroplasticity device training so my muscles nervous system and brain get lots of activity.
I've recently started Oxygen contrast saturation level training... 85 percent- high blood oxygen cycles with 13 percent- low blood oxygen and have been able to do vigorous exercise and have stability in my normally overly hyper active connective tissues.

This week i will get an IV after my O2 training which one doctor says offers the best results in a video ( i do not know this doctor). I will experiment with glutathione IV , with NAD IV and with the combo and then combo of shots. Right now, I'm just getting aquatinted with doing these training sessions at home.

 

[Learner1]

@Learner1 also responded well to NAD+ infusions. You can ask her how quickly her response was

I do a regular "mito cocktail" infusion, used to be weekly, now every 2-3 weeks. NAD+ is a component and it is added at the end if a bag of mito nutrients, before bags with glutathione, resveratrol, and sometimes phosphatidyl choline.

Do you feel that the glutathione infusions are essential following NAD+ infusions? To get the benefits of NAD+?

No, they are useful to reduce oxidative stress. The NAD+ is to produce more ATP and fir the other benefits of NAD+.

What are the dosages for the glutathione subq shots and IVs? Glutathione shots were once popular around here ~8-10 years ago. But many said it required ATP to be in the shot as well, to get the glutathione intracellularly.

I get 3-4g glutathione per IV. However, thus can backfire, as one will get a diminishing return from glutathione unless you also take nutrients that support recycling it, including:

Vitamin C
Calcium Gluconate or Chloride
Magnesium Sulfate or Chloride
Zinc Chloride
Selenium
B-100
MB-12
5-MTHF
B-5
B-6
Sodium Bicarbonate

I didn't even know there is direct ATP supplementation... does that help at all? Or just for the transport

AMP us available in Canada, but not the US and I hear it works well. I've never seen it heard of ATP IVs.

If NAD+ didn't help. You should try NADH

both substances cost close to nothing from laboratories. The US health clinic prices are probably due to the many hours per IV.

1500mg NAD+ costs about 20USD max in bulk orders from licensed labs (as a doctor)

NAD+ costs more than that in the US from compounding pharmacies. I gave nit seen IV NADH available.

as private person you can source from China and have it 3rd party lab tested yourself in the USA.
1500mg NAD+ for about 10USD and 250USD lab testing once for the whole supply

i wouldn't suggest to do this without a doctor or nurse that is qualified to filter the substance and constitute it etc.!!!!

NAD+ is the most difficult IV I've done. I usually can't make it through without Benadryl and it has to be dropped very slowly. There are very specific instructions given by the pharmacies before they'll sell it, typically. IV anything is not a DIY project. If you are introducing anything into the veins, it must be clean and uncontaminated, and sterile procedures must be followed. I've heard of very bad reactions, even fatal, when steps were skipped.

 

[Learner1]

Depends on how I feel. I'll do a 1000 or a 750 or a 300mg IV. But with shots it's just two with combined amount 200mg.

That is a huge amount. My guess is that if you need that much, something else needs fixing. Also, mire us not better. Too much can promote the growth of cancer...

Nicotinicamide Riboside is oral and does the same thing. No need for expensive infusions.

NR is not the same. It requires converting to work. Not all people, myself included can convert it.

And, there is a great difference from the NAD+ IV and oral. The IV works instantly and lasts for about 36 hours for a dose. Oral, taking sublingually, lasts maybe 6 to 8 hours for the same dose.

Yes, I tried NAD+ infusions. I did two sets of 10 infusions, with 5 infusions/week (M-F). My highest dose was 1,000mg. The NAD+ comes in 500mg vials. And the various protocols have different number of vials per day (starting higher then tapering towards the end.)

This is a protocol for addicts. It makes them feel better so that they can get off of whatever they're on. It is not a protocol for sick people. Again, more is not better. My protocol is to do a little bit, 100-200mg, only weekly or bi-weekly basis, to raise my function consistently over time. Not blast my system with overkill, and then let it wear off... This doesn't seem natural, unless to get somebody out of a crisis. I wanted to improve my function gradually over time, which is what's been happening.

I was VERY sensitive to the rate of infusion. So much so, that if I switched from my desk chair to the couch (so height from heart to drip increased, thus faster infusion rate due to lower venous pressure), I would get sudden side effects.

Agreed. I accidentally got a double dose this past week - the formula that came in was twice as strong, and almost instantaneously I felt a burn in my forearms and legs and temples. It was really unpleasant.

DID you notice any BENEFIT or improvement? And how "fast" did these occur?

I've gotten a long slow steady benefit over time. I've been feeding my mitochondria other nutrients and the NAD+ helps to give my metabolism energy to run everything, so my goal has been to slowly improve the quality of my mitochondria over time and have them work better.

I did not see any benefit or improvement from doing IV NAD+. But I still think it was worth doing because it does help on a cellular and DNA level. I sometimes wonder if perhaps my 2 sets of 10 days of infusions were just not enough. That my NAD+ levels were so low that I just needed to do more infusions. But from the anecdotes and protocols online, most people see a response very quickly. There may be a proglem with NAD+ recycling as it does get consumed quickly and needs to be recycled. Perhaps that is why it didn't work. But I didn't really investigate NAD+ recycling. I'm taking oral NAD+ and NMN daily now.

Again, I believe it's slow and steady wins the race. Not applying a huge blast of NAD+ to overwhelm damaged mitochondria, and then slacking off. So, I've had this protocol where I've done the IV once every 1 to 3 weeks and then have been doing NMN sublingually daily. Over time, I've gradually improved. I'm not cured, nor do I know if I ever will be, but the NAD+ and NMN are definitely factors that have helped.

 

[mitoMAN]

Good points @Learner1
Please don't do I.V.s yourself without a doctor or nurse. My statement wasn't meant as encouragement to do so.

I am wondering if there is official NMN I.V or S.C. in the US Health Clinics?
Almost all the promising studies are done with I.p injecting NMN in animals. Only a small portion uses oral NMN.

but I have yet to read anything about human use of I.V./I.M./S.C. NMN

I started doing 300mg NAD+ the last three days.
Contrary to 300mg NADH this one really gives all the symptoms described in I.V administration by the other guys on here. Slight dizziness and sickness for about an hour after injection etc.
I had to split the NAD+ in 2x 150mg

however:
the NADH is building up quite nicely I have the feeling.
Currently about 4-5 hours less in bed per day when I do the injections.
Also my brain works normally again which is a great sign for me that NADH is doing something good for me.

 

[Learner1]

but I have yet to read anything about human use of I.V./I.M./S.C. NMN

I haven't seen any either, but found this in IV NAD+ which is interesting...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751327/

 

[mitoMAN]

I haven't seen any either, but found this in IC NAD+ which is interesting...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751327/

if I understand the study correctly:

only the First 250mg of NAD+ were completely transported into the cells (first 2hours)

afterwards the NAD+ was "only" broken down into its metabolites NAM, NMN etc and NAD+ was quickly urinated as well.

so the main NAD+ intracellular transport was saturated after 250mg


Another reference:
"In vitro, intracellular NAD+ increased upon exposure of cell lines to exogenous NAD+ whereas NAD+ precursors could not reproduce the effects of exogenous NAD+ and were not found in the medium, suggesting direct cellular uptake. In mitochondria exposed to exogenous NAD+, NAD+, NADH and O2 consumption and ATP production were increased while DNA repair was unaltered (Pittelli et al., 2011). "

 

[mitoMAN]

On a sidenote of possible NADH effects:

Reference: https://sci-hub.tw/10.1139/apnm-201...d4OgcJRKSHenxJyt6DE_Cuuo2JIwoCDaC_IQ7Wg82cK8w

Immunemodulatory effects:

NADH is known to be important to restore depleted cellular stores of ATP (Forsyth et al.,
1999). Our study showed a stimulatory effect of NADH on lymphocyte proliferation, with a
significant increase in IL-4 levels, without affecting IL-2 levels in both aged and young men
and women. NADH appeared to have generated a Th2-like phenotype. Stimulatory effects of
NADH on cell growth seemed to be related to increasing cellular ATP regeneration, since
ATP plays a key role in cell proliferation, and T-cells require high levels of NADH
(Delmastro-Greenwood and Piganelli, 2013)

Reducing Oxidative Stress and MDA, increasing total Glutathione by acting on SIRT2

In the presence of NADH, lymphocyte GSH levels
and catalase activity were enhanced, while MDA and carbonyl proteins were reduced in the
elderly, reflecting a diminution in intracellular oxidative stress. Multiple studies have
implicated NADH as an antioxidant (Olek et al., 2004). Recently, Cao et al. (2016)
demonstrated that in vitro treatment of PC12 cells with 1mM of NADH induced an increase
in the levels of nuclear Nrf2, catalase activity, and total glutathione by acting on sirtuins
(SIRT2).

Might explain the big effect I have from injectible NADH as my MDA-LDL is very high, oxidative stress is VERY high, and I am having a TH1 dominance.
Just some thoughts on my personal reaction to NADH.

 

[triffid113]

I take a lot of supplements which put me in the pretty healthy range, (from very unhealthy, 18 broken genes) so not coming from the same place as y'all, but I added this year 1 gram niacinamide to my protocol for thie following reason and with the following results:

I noticed my skin was starting to look and feel rough and I remembered that when I experimented in college that niacinamide causes softer skin. I took 500mg niacinamide and also 1/day of life extension's niagen (NAD+) product. After about 5 days, my skin no longer looked rough and felt softer. I also noticed that the sun, which had felt harsh to me, now felt great. I looked it up and niacinamide provides uva anf uvb protection. Aftet 1 bottle of each, I was able to lift the arm with the bad shoulder joint (not saying the joint repaired, it still snaps the nerves). I then looked online and decided these supplements were both equivalent precursors for NAD+. Yes, I know niacinamide was early reported to interact negatively with sirtuins, but that was found to happen mainly in vitro. In vivo, this only happened at the outset after which niacinamide reacts favorably with sirtuons to increase lifespan. So, niacinamide is cheaper. I take a gram a day (I doubled the dose when I diidn't reorder niagen)

Did not notice more energy on a macro level, but my SKIN did (that is how the uva and uvb protection is achieved... more ATP (energy) in the skin to replace that depleted by sun.

Hope this helps.

 

[Learner1]

I understand the study correctly:

only the First 250mg of NAD+ were completely transported into the cells (first 2hours)

afterwards the NAD+ was "only" broken down into its metabolites NAM, NMN etc and NAD+ was quickly urinated as well.

so the main NAD+ intracellular transport was saturated after 250mg

I'm not sure that is the correct interpretation. Yes, about saturation of 260mg after 2 hours, but everything after that didn't get urinated out.

"plasma NAD+ levels failed to rise until after the 2 h time point reaching a maximum of ~400% above baseline for NAD+ and metabolites NAM, meNAM and ADPR (398%, 409%, 393%, respectively) only at the 6 h time point (Figures 1A–E). This was internally consistent with the peak of urinary excretion for both NAD+ and meNAM also occurring at 6 h before rapidly decreasing after the end of the infusion"

In vitro, intracellular NAD+ increased upon exposure of cell lines to exogenous NAD+ whereas NAD+ precursors could not reproduce the effects of exogenous NAD+ and were not found in the medium, suggesting direct cellular uptake. In mitochondria exposed to exogenous NAD+, NAD+, NADH and O2 consumption and ATP production were increased while DNA repair was unaltered (Pittelli et al., 2011).

First, this is in vutro, where in Vivi night be different. Second, this is a 10 year old study in a very fast developing field.

At any rate, the most I get in an IV is 200mg. I am not convinced more is better, and it can potentially drive cancer if you have a few mutated cells hanging around. I suspect if you need that much more, you likely have other problems...my mitos are not too spunky and I get a pretty hefty benefit out of 125-200mg.

On a sidenote of possible NADH effects:

Reference: https://sci-hub.tw/10.1139/apnm-201...d4OgcJRKSHenxJyt6DE_Cuuo2JIwoCDaC_IQ7Wg82cK8w

Immunemodulatory effects:
Reducing Oxidative Stress and MDA, increasing total Glutathione by acting on SIRT2
Might explain the big effect I have from injectible NADH as my MDA-LDL is very high, oxidative stress is VERY high, and I am having a TH1 dominance.
Just some thoughts on my personal reaction to NADH

However,vhavubg a high MADH to NAD ratio is not good. You want it the other way around. Ivve found that BAD will convert to NADH as needed.

I took 500mg niacinamide and also 1/day of life extension's niagen (NAD+) product.

Niagen is not NAD+. It is the precursor, nicotinamide riboside, which some of us cannot convert at all. Taking NMN or BAD+ is more direct. Nicotinamide has to go through multiple conversions to get to NAD+.

One caution about overloading with ANY form of niacin - it can reverse methylation x so you may need to increase folate, MB12 and/or TMG to compensate.

I know niacinamide was early reported to interact negatively with sirtuins, but that was found to happen mainly in vitro. In vivo, this only happened at the outset after which niacinamide reacts favorably with sirtuons to increase lifespan. So, niacinamide is cheaper. I take a gram a day (I doubled the dose when I diidn't reorder niagen)

You get what you pay for. Niacinamide is cheap, may not convert to where you need it to go, and Jay reverse methylation, affecting DNA copying, immune function, neurotransmitter production, and having an unwanted effect of promoting cancer.

Sounds like you lucked out, but others might want to be cautious.

 

[triffid113]

Hm. Well niacinamide was reported 40 years ago to help delay diabetes, which runs in my family. I always felt it was a good supplement for me and with (then surprising) good effect on skin. idk about methylation effects and how quickly one could recover if incurred, but u could tell if t was doing positive things in 5 days. I loosely follow Freddd's protocol for methylation and do alright per homocysteine and MMA tests. I... don't do as good as I should cuz too many pills. I let my homocysteine sit at 9 or 10.

 

[Learner1]

Freddd seems to have a very unique genetic setup which seems to differ from most people around here, do following his protocol may not be the wisest idea. Ideally, a comprehensive nutrient test which shows what the various pathways are doing, like a Genova diagnostics NutrEval, would be wise.

Methylation is essential for proper immune function, neurotransmitter production, and proper copying of DNA, which if not working properly could lead to cancer. As a stage three cancer survivor, I learned the hard way that this is essential A homocysteine level of 9 to 10 is not optimum. Somewhere around 6-8 is better. Directly getting in the way of methylation by overuse of niacinamide without compensating might not be wise.

And, type 2 diabetes is mostly related to high carbohydrate diets. Avoiding diabetes with a healthy, lower carbohydrate diet, is likely the best strategy, rather than depleting oneself of methyl nutrients.

 

[Hopeful2021]

On a sidenote of possible NADH effects:

Reference: https://sci-hub.tw/10.1139/apnm-201...d4OgcJRKSHenxJyt6DE_Cuuo2JIwoCDaC_IQ7Wg82cK8w

Immunemodulatory effects:


Reducing Oxidative Stress and MDA, increasing total Glutathione by acting on SIRT2

Might explain the big effect I have from injectible NADH as my MDA-LDL is very high, oxidative stress is VERY high, and I am having a TH1 dominance.
Just some thoughts on my personal reaction to NADH.

@mitoMAN @Learner1 (per comments on inflammation, the urine results study, dose amount, and older comments on burning)

I can pass along a tidbit from my doctors observation. Those ppl who have less inflammation do do better with NAD IV.

As to some of the thoughts in dosage... for the brain and nervous system of ppl with Parkinson's, frequency and dose that is higher do matter.

I'm not worried about these studies about urinating out nutrients. From our breathing biochemistry to our nutritional status to our glucose and other hormones, the kidneys do what they do to help. So theres more than this study's conclusions to consider.

I know when I'm crashing and my brain is having lots of problems, it's very important for me to work my way up to 1,000mg of NAD IV. That a shot or nasal spray won't help me enough.

I'm currently much stronger than I've been in 20 months. I'm very thankful and appreciative of being able to have had my months of mainly doses at 500-1,000mg of NAD.

I'm on drip now today of only 300mg though. I'm doing oxygen desat and saturation training and seeing how an IV of NAD then followed by an IV of glutathione will help me.

My work, my many hours retraining my nervous system and muscles to be stronger along with my weeks and weeks of NAD IV have shown me that the parts if tge nerve-muscle connections that currently need tge most help are the ones that appear in the brain-body map.
So if parts of the leg muscles burn, then that's where your attention will go as nutrients and hormones and just the gazillion types of biochemical reactions that are at work to help heal.

I discovered early on as we increased my dose of NAD that moving around helped. Firstly, that being hooked up to the IV actually gave me energy TO MOVE around was remarkable in and of itself. Then, movement taight me that i could help those parts i was moving or tge connective tissue patterns i was engaging to be stronger for several hours AFTER the IV.

Because i had a tremendous amount of hyper mobility and instability in my neck skull throat jaw patterns, i would also get perineural shots or later PRP shots but not deep, just Perineural style. Then those sites woukd have extra benefits of days or a week plus with PRP.

So it really depends in what you are dealing with and willing to push or explore. I started IV nutrients to get some type of stability in all those areas so that i could swallow and drink and stop gagging and have stable airway opening. Then to be able to withstand the vibration of riding as passenger in car to get IV. Then to be able to have less swallow and airway problems. Eventually I progressed to wanting energy to walk again more than to just shuffle from bed to bathroom to kitchen and such.

Now, I'm still doing IV for my brain ... but also to mount a level of healing to be free of this disease permanently.
Every increment has afforded me some bits of knowledge. This base lets me apply for myself that Options and trial and error are really important to embrace.

Tomorrow I will do only a small bag of nutrients and a 2,000 mg IV of glutathione after I do a morning session of my desaturate / then saturation oxygen training. My doctor and i will explore 2 consecutive days of IV glutathione (small bag of nutrients before) as per what was shared in the video on YouTube of another doctor sharing about great benefits of O2 and IV glutathione.

That video is one I shared in my post about oxygen earlier. I'm more than ten years in this disease and really really am ready to live well and vibrantly without it ever again.

I've far exceeded what results I wanted to get in the beginning from IV therapy. What i have learned this past 20 months from reading about other's stories is that it is at the 6 month mark where improvements that last are to be had. I've often stopped at 2 months or at 3 months. Now, for the next 3 years, I'll be pursuing getting rid of this disease forever for myself.

And there are many days when I don't want to push myself to do the program I've set up. Like this morning, I did not want to get out of my warm bed to go turn on the oxygen concentrator. But it is the thing now that let's me walk without discernible calculation that I am even using energy. That is a huge benchmark of improvement from having a spoon debt to counting and debating how spoons will be used to not even recognizing that spoons or energy of any kind is being utilized.

 

[Learner1]

My question would be why you are using such enormous doses of NAD+? I have no idea how you can stand that big an infusion, which must take many hours and be pretty expensive.

Have you looked into peroxynitrites, damage to mito membranes and other mito nutrients?

And, for most people, that high a dose might promote cancer....

Glad it's working for you, though.

 

[mitoMAN]

A little Update on my research concerning Injectible NMN and NADH:


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277084/

COMPREHENSIVE INVITED REVIEW Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes Nady Braidy,1 Jade Berg,2 James Clement,3 Fatemeh Khorshidi,1 Anne Poljak,4,5 Tharusha Jayasena,1 Ross Grant,2,5,6 and Perminder Sachdev1,7


NMN:

For instance, using an high-performance liquid chromatography (HPLC)-based method, intracellular concentrations of NMN and NAD+ were reported to increase up to 500 pmol/mg and 50 pmol/mg of white adipose and pancreatic tissue 15 min after intraperitoneal injection of 500 mg/kg of NMN (376)



However, NMN injections led to significant increases in NAM levels in plasma, which suggests that NMN may be partially converted to NAM following intraperitoneal injection. The presence of NAM in mice plasma following NMN injection suggests that NMN may be initially converted to NR (272).



NADH:

Oral supplementation with NAD+ and NADH has not shown any significant elevation in plasma or tissue levels of NAD+ , potentially due to inefficient metabolism of NAD+ through the gut, thus leading to poor bioavailability (177). In addition, oral NADH may not be oxidized to NAD+ in the body, may not be efficiently absorbed by the gastrointestinal system, or may be converted to a product before absorption that cannot yield NAM (34, 35)



NAD+ serves as an electron acceptor, and its reduction leads to the generation of NADH, which can be subsequently oxidized by complex I of the ETC to produce NAD+
The cytosolic/nuclear NAD+ pool is replenished when NADH is converted back to NAD+ in the reactions of the aforementioned shuttles, including the conversion of pyruvate to lactate. NAD+ levels in nuclear, cytosolic, and mitochondrial compartments are also replenished via specific de novo and salvage pathways that are discussed in the text and overviewed in Fig. 2. Within mitochondria, NADH is oxidized to NAD+ in the electron transport chain (ETC).



One study investigated the effect of NADH, the reduced form of NAD+ , on proliferation, cytokine release, and cell redox status of lymphocytes collected from healthy aged subjects (40). Cells exposed to NADH (500 lM/L) showed increased levels of GSH, and catalase activities, while malondialdehyde and carbonyl proteins are markedly decreased (40), suggesting a decline in oxidative stress. Recently, it has been shown that treatment with 1 mM NADH increased the expression of nuclear Nrf2, catalase activity, and total GSH by increasing SIRT2 function (69).



The reduced form of NAD+ and NADP are NADH (Fig. 2, Step t) and NADPH (Fig. 2, Step s), respectively. These nucleotides serve as hydride donors, in over 400 enzymatic reactions throughout the body involving dehydrogenases, hydroxylases, and reductases (219). These reduced and phosphorylated forms can interconvert, but do not alter the levels of NAD+.



Supplementation with either NAD+ and its reduced form NADH or its precursors represents a potential therapeutic strategy to slow down the aging process and/or improve the management of age-related degenerative disease.

We found that NADH dose-dependently increased the levels of GSH, GSSG, and total glutathione (Fig. 3A). The time-course study regarding the effects of NADH treatment on glutathione synthesis showed that NADH increased the GSH and GSSG levels at both 8 and 12 h after the NADH treatment (Fig. 3B), while it did not affect the GSH and GSSG levels at either 2 or 4 h after the NADH treatment


Caution:
Multiple studies have also suggested that NADH can affect the oxidative stress state of cells. For example, NADH can produce direct antioxidant effects, while excessive intracellular NADH can induce ‘reductive stress’ [23–25]. Our previous study has also indicated that NADH treatment can increase the intracellular oxidative stress and decrease the survival of glioma cells, which can be prevented by antioxidants [26]. Other studies have suggested that NADH may produce beneficial effects on PD [19,27].

>> It seems like that NADH can indeed have a double edged effect like many other substances. Poor antioxidant supplementation and "solo" NADH Injections could backfire.

For me it is working like a magic pill while it could harm others. Please apply this information with caution.
Possibly my NADH was depleted while others have a surplus and NAD+ deficency. In that case, it might not be of any benefit. But thats just pure speculation from my side.

 

[mitoMAN]

I'm not sure that is the correct interpretation. Yes, about saturation of 260mg after 2 hours, but everything after that didn't get urinated out.

Sorry I didnt mean to say everything gets urinated out. Indeed the NAD+ gets broken down to its metabolites which is a good benefit to have elevated NMN (NAM maybe not so much) which can then be converted to NAD+.
After about 4-5 hours the urination of NAD+ gets very high which could be interpreted at having reached a possible saturation that doesnt need any further exogenous NAD+ supply.

But the main absorption of extracellular to intracellular NAD+ seems to happen the first two hours (260mg) and then seems to get to a saturation point. Thats what I was pointing towards.

So indeed I personally think that your approach of doing 200mg I.Vs is smart and would maximize the NAD+ benefits vs a possible overdose with side effects.
Personally, I dont notice any positive effect of 300mg NAD+ on the same day.
Versus huge positive effect 30min after NADH injection.

However,vhavubg a high MADH to NAD ratio is not good. You want it the other way around. Ivve found that BAD will convert to NADH as needed.

This is correct but I have yet to find a study that goes into detail about what happens with excess extracellular NADH in case of high intracellular NADH (which i tried to research in the above post).

Most studies I have found on NAD+:NADH ratio referred to a NAD+ depletion.
In theory - I was hoping that NAD+ supplementation will prevent a NAD+ depletion.
But extracellular NADH has the possiblity to convert back to NAD+ if needed.
Which lessens my worry about creating a NAD+ depletion FROM NADH administration.
I personally see this as a possible reduction of exogenous NADH to NAD+ in case of NAD+ deficency.


NADH oxidation to NAD+ back and forth:

Its ability to switch between these two forms is what allows NAD to carry out its main function—carrying electrons from one reaction to another in the process of metabolism and energy production.

The electron transporters embedded in the mitochondrial membrane are oxidoreductases that shuttle electrons from NADH to molecular oxygen, another electron acceptor. This loss of electrons is called oxidation. NADH undergoes a reverse reaction, converting back to NAD+
If oxygen is present, the cell can extract substantial chemical energy by breaking down pyruvate through the citric acid cycle, which converts NADH back to NAD+. Without oxidation, the cell must use fermentation to oxidize NADH before it builds up to unhealthy levels.

See NADH Oxidation Cycle within Mitochondria during Excercise creating depeletion and surplus of each NAD+/NADH constantly:

The cytosolic/nuclear NAD+ pool is replenished when NADH is converted back to NAD+ in the reactions of the aforementioned shuttles, including the conversion of pyruvate to lactate. NAD+ levels in nuclear, cytosolic, and mitochondrial compartments are also replenished via specific de novo and salvage pathways that are discussed in the text and overviewed in Fig. 2. Within mitochondria, NADH is oxidized to NAD+ in the electron transport chain (ETC).

If you have more detailed insights on this I am very curious to learn more about the NAD+ / NADH cycle.

 

[Learner1]

Thanks for your research. I'll attach these that I've been collecting. I haven't reread then lately, but you might find some nice insights...

https://www.sciencedirect.com/science/article/abs/pii/S0891584913000051?via=ihub

 

[Learner1]

The NADPH piece can be problematic. If one has high homocysteine, oxalates, overactive mTOR, allergens, too much dopamine, sulfites, glutamate, mycotoxins, Lyme, too many EMFs, or toxic exposure causes overstimulatiin of the NADPH oxidase e, creating overproduction of:

• Superoxide radicals
• Peroxynitrites
• Mast cell degranulation
• Histamine
• Glutamate

This depletes glutathione and interferes with phase I detox, recycling of antioxidants, and creates a vicious cycle. So, it's not so easy as the theory...

 

[triffid113]

Freddd seems to have a very unique genetic setup which seems to differ from most people around here, do following his protocol may not be the wisest idea. Ideally, a comprehensive nutrient test which shows what the various pathways are doing, like a Genova diagnostics NutrEval, would be wise.

A homocysteine level of 9 to 10 is not optimum. Somewhere around 6-8 is better. Directly getting in the way of methylation by overuse of niacinamide without compensating might not be wise.

And, type 2 diabetes is mostly related to high carbohydrate diets. Avoiding diabetes with a healthy, lower carbohydrate diet, is likely the best strategy, rather than depleting oneself of methyl nutrients.

Thanks. Per your post, I will take another homocysteine test to see what niacinamide is doing to methylation. I know 10 is not optimal. I just take so many pills that I frequently verge on nausea. (Morning coffee plus pills = disaster). I have so many broken genes that it takes this to get mine down ro 6.3 (and methylation is far from my only health issue!): Thorne Basic B 2/day. 1 g. TMG. 50mg P5P. Some sublingual B12 (used to be B Right). I haven't taken the sublingual B12 in a very long time...my cobalt was getting high! I also rarely take the TMG, though I know I need it because it works faster than B12+folate to keep homocysteine low after meals. I usually only do the Basic B 1/day. I always do the P5P though since it is also used to make stomach acid, which I don't make enough of. And it helps spare your kidnies from things like homocysteine.

I was curious if u have any idea why a niacin precurser would affect methylation.

Incidentally, it was noted here at one time that adequate methylation takes care of bug bites. If your bug bites itch more than 20 minutes or so, you may not be getting adequate methylation. If I start noticing alot of itching due to bug bites, I take that extra Basic B for sure.

I have eaten low carbs my whole life. What works for me though is supplemental zinc. Studies have shown all diabetics are low in zinc, and zinc is used to make insulin.

Thanks. Be cautious everyone.