NAD+ vs NADH

Swim15

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So I understand the differences here but don't see NADH talked about much or offered as infusions like NAD+ is...that's a little confusing to me seeing as NADH is the reduced and higher energy form and seems to me like it could drive energy production more than NAD.

Has anyone got experience comparing the two and, specifically, infusions with NADH? Thinking about trying it and seeing if it has effects that are different than NAD
 

mitoMAN

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NADH can enter the Blood Brain Barrier and thus was mostly used for Parkinsons and Alzheimer to give an immediate boost. I only benefit from NADH myself (especiallyas brain fog buster) but dont benefit from NAD+ at all.
Other people are the opposite way around. You will have to try it yourself I think.

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





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+.


In Excercise:

Without oxidation, the cell must use fermentation to oxidize NADH before it builds up to unhealthy levels.

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).





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].
 

Learner1

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@mitoMAN What dose did you try of NADH vs NAD+?

NADH works for me, but a 20mg dose didn't do much, and only lasted a couple hours, but a 125mg dose of NAD+ or NMN lasts most of the day and 100mg NAD+ IV lasts about 36 hours.

NADH is also pretty expensive. It's US$1.02 per 20mg pill, or $6.12 for 120mg vs $.42 for 125mg NAD+ sublingual tablet.
 

mitoMAN

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for NADH tablets I had tried the original from Prof Birkmayr (who ran most of the studies) from 20-200mg sublingual with zero effect.
With NADH Injections I noticed a VERY strong effect once I hit 150mg subq.

With NAD+ Injections I noticed no improvements ranging from 100-1800mg subq.

With NMN 1000-2000mg orally I notice zero effects. Took 500-2000mg over 5 months.
(legit source Doublwood NMN)

I think a new study found that people without a certain microbiom enzyme cant process oral NMN.
I took it sublingual as well without effect.

I am paying 7$ per 1000mg NADH crystalized powder.
We are currently lab testing it for purity and heavy metal contents.
 

Learner1

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With NADH Injections I noticed a VERY strong effect once I hit 150mg subq.

With NAD+ Injections I noticed no improvements ranging from 100-1800mg subq.

With NMN 1000-2000mg orally I notice zero effects. Took 500-2000mg over 5 months.
(legit source Doublwood NMN)
Never heard of Doublewood.

However, you are talking about very high doses. One concern is that if one has mutated cells (as most people do to some degree), adding a large amount of an NAD product could be like throwing gasoline on a fire and causing cancer proliferation. Though it can be helpful, too much of a good thing can be bad.

NAD+ also has important implications in cancer and its availability affects cell proliferation, invasion and tumor growth14. ... This may indicate that when deprived of NAM as the main NAD+ source, cancer cells have an ability to utilize other NAD+ biosynthesis pathways46,47

From: "Extracellular NAD + enhances PARP-dependent DNA repair capacity independently of CD73 activity | Scientific Reports" https://www.nature.com/articles/s41...dicate that when,+ biosynthesis pathways46,47.

In my experience, if you need that much, it's likely there are other problems that need to be solved first. The body may be fine regulating energy production, e.g. hibernating and hunkering down until the threat passes.... Or, using another analogy, adding gas to a broken engine and driving it faster won't make it run better and may lead to worse problems.

I find that 125mg of NAD or NMN are very helpful. You've noted in other threads you do have some significant abnormal test results, and maybe it might be fruitful to attend to those. I know its been helpful for me to do so.
 
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I am paying 7$ per 1000mg NADH crystalized powder.
We are currently lab testing it for purity and heavy metal contents.
Sorry to revive such an old thread but can I ask if you ended up finding a source that tested well?
 
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