17 replies to this topic

[samstersam]

http://www.vice.com/...usion-injection

 

I am currently taking NR to boost my NAD levels.

 

Apparently there is a new therapy in UK that costs 500 and is an injection based NAD booster.

 

Any thoughts?

 

edit: Not sure if this belongs in Telomeres subforum

Edited by samstersam, 21 October 2016 - 04:41 PM.

[sthira]

Thanks, this is interesting, and seems obvious that infusions would be more effective than swallowing more pills. I wonder if it's safe long term, if it offers repair opportunities for the body, if it's placebo, or if it's like putting rocket fuel into damaged machinery? That is, maybe it'll speed us up, but do or do not NAD injections repair damage seems like an important question.

Edited by sthira, 21 October 2016 - 05:49 PM.

[mrkosh1]

http://www.zenhealth...nad-iv-infusion

 

Since NAD+ in the blood stream has to be converted to NR before entering cells, I'd be much more interested in an infusion of NR.

 

My guess is that a relatively high dose of NR for a few days would be equally as effective at probably 1/50th the price. To get a really rapid dose of NR, I wonder if dissolving it in water and drinking it on an empty stomach would be of help?

[Heisok]

mrkosh1,

 

In a thread started by Turnbuckle titled "A protocol to upgrade mitochondria" where they outline some trials,

Fafner55  recently trialed a protocol which used very high doses of NR for several days. They seemed encouraged by their initial results, but they have not given a recent update.  I have been curious

 

http://www.longecity...chondria/page-2

[Turnbuckle]

I for one believe that NR has been hyped to sell a very expensive supplement to the public when a very cheap one will do the job. It's not clear to me that NR is actually better than nicotinamide for doing what we want--which is to get rid of dysfunctional mitochondria. This appears to require that the ratio of NAD+/NADH be increased to get the cell's quality control machinery into motion, not just the absolute level of NAD+. This paper gives some insight--

 

 

Capsule

 

Background: Nicotinamide treatment decreases mitochondrial content and helps cells maintain high mitochondrial quality.

 

Results: Metabolically enhanced NAD+/NADH ratio and chemically induced SIRT1 activation similarly decreased mitochondrial content, increased autophagy, and induced mitochondrial fragmentation.

 

Conclusion: Mitochondrial content is modulated by high NAD+/NADH ratio and mechanisms that involve SIRT1 activation.

 

Significance: Elevation of NAD+/NADH ratio may promote cellular health by facilitating mitochondrial autophagy.

 

http://www.jbc.org/c...7/23/19304.long

 

 

 

 

 

Nicotinamide increases NAD+ and increases the ratio very nicely. NR also raises NAD+, perhaps more than nicotinamide, but I haven't seen anything to date that mentions the ratio. It's also not clear how much you will have to take of NR, but it will definitely be a good deal more than the marketing suggests if you want to achieve the 2.7 fold increase in NAD+ that the primary researcher of this product speaks of--

 

Nicotinamide riboside (NR) is in wide use as an NAD+ precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD+ metabolism in humans. We report that human blood NAD+ can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD+ with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD+ metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD+, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD+ repletion.

 

https://www.ncbi.nlm...pubmed/27721479

 

 

Presumably the 2.7 fold increase is associated with the gram dose (or higher) of the researcher himself (thus an n=1), and the rise of NAAD is a concern, as it's not known what this might do to the process, especially as it was increased by a factor of 45. The surprisingly preliminary state of the NR research is evident in the following story published just days ago--

 

 

The new research, reported Oct. 10 in the journal Nature Communications, was led by Charles Brenner... Brenner is ... co-founder and Chief Scientific Adviser of ProHealthspan, which sells NR supplements under the trade name Tru NIAGEN®.

 

The human trial involved six men and six women, all healthy. Each participant received single oral doses of 100 mg, 300 mg, or 1,000 mg of NR in a different sequence with a seven-day gap between doses. After each dose, blood and urine samples were collected and analyzed by Brenner's lab to measure various NAD+ metabolites in a process called metabolomics. The trial showed that the NR vitamin increased NAD+ metabolism by amounts directly related to the dose, and there were no serious side effects with any of the doses...Prior to the formal clinical trial, Brenner conducted a pilot human study -- on himself.

 

https://www.scienced...61010135418.htm

 

 

 

Note the strong conflict of interest. My own experience with NR and nicotinamide suggests that nicotinamide works very well when taken at a dose of a gram three or four times a day (which I don't do every day, but only intermittently) and adding 100 mg NR to each gram dose didn't seem to make it better. Nor was 500 mg NR by itself as good, though at the gram level it might have been as good or better. I can't say as I didn't try that dosage, and there wouldn't have been any point as I didn't see any reason to take a very expensive supplement over a very cheap supplement if I have to use the same dose. 

 

Still, a direct NAD+ injection (if that's what it is) sounds very interesting. That it's called a "cocktail" suggests that it's not NAD+ at all, but some mix of precursors. 

 

Edited by Turnbuckle, 27 October 2016 - 11:36 AM.

[tunt01]

I for one believe that NR has been hyped to sell a very expensive supplement to the public when a very cheap one will do the job. It's not clear to me that NR is actually better than nicotinamide for doing what we want--which is to get rid of dysfunctional mitochondria. This appears to require that the ratio of NAD+/NADH be increased to get the cell's quality control machinery into motion, not just the absolute level of NAD+. This paper gives some insight--

 

Nicotinamide increases NAD+ and increases the ratio very nicely. NR also raises NAD+, perhaps more than nicotinamide, but I haven't seen anything to date that mentions the ratio. It's also not clear how much you will have to take of NR, but it will definitely be a good deal more than the marketing suggests if you want to achieve the 2.7 fold increase in NAD+ that the primary researcher of this product speaks of--

 

 

Interesting paper.  I'll have to give it a read this weekend.

 

What about the idea that Nicotinamide inhibits SIRT1 ?

 

I found the statement from Brenner (in the interview w/ Bryan), that NRK enzyme activity is upregulated in tissue that is "niacin deprived" to be interesting.  However, it's probably the case that NAMPT and other pathway components similarly upregulate based on some allosteric regulatory factor.

[Turnbuckle]

 

 

 

What about the idea that Nicotinamide inhibits SIRT1 ?

 

 

 

 

Does it matter as long as it does what you want it to do? From this paper, it seems that around 20% of the mtDNA mass can be eliminated by one day of nicotinamide treatment. See Fig. C below--

 

 

 

This result is quite interesting, as mitochondria make up some 10% of the body's mass. So if 15% of the mitochondria mass is eliminated in one day (from Fig. A, above, and ignoring that some mitochondria aren't susceptible--such as those in platelets), and this is built back up by taking PQQ and other supplements on day 2, then a good deal of energy will be required to first digest 1.5% of the body's mass, and then another great deal of energy to synthesize new proteins to make new mitochondria. So not only could you conceivably improve your mitochondria, but you could lose weight in the process, assuming you could apply this treatment over and over and it continued to work as above.

Edited by Turnbuckle, 27 October 2016 - 06:24 PM.

[mrkosh1]

First of all, the brain boosting cocktail was composed of NAD+, vitamin C, some herb if I remember correctly, and B-12. The extra methyl groups could have been a good idea if the dose was very high. But there were no other NAD+ precursors.

 

Secondly, high levels of nicotinamide by itself can suppress the SIRTS. The activation of the SIRTS are what we need for anti-aging potential and healthy mitochondria.

 

Thirdly, Nicotinic Acid is a good precursor of NAD+ (not as high as NR) but causes flushing.

 

 

[Turnbuckle]

First of all, the brain boosting cocktail was composed of NAD+, vitamin C, some herb if I remember correctly, and B-12. The extra methyl groups could have been a good idea if the dose was very high. But there were no other NAD+ precursors.

 

Secondly, high levels of nicotinamide by itself can suppress the SIRTS. The activation of the SIRTS are what we need for anti-aging potential and healthy mitochondria.

 

Thirdly, Nicotinic Acid is a good precursor of NAD+ (not as high as NR) but causes flushing.

 

Two questions:

 

You said above that NAD+ has to be converted first into NR, so do the other ingredients in this cocktail have some function in getting it into the cell unmodified? And second, if nicotinamide can reduce mtDNA mass as shown in Figure C I referenced above, then wouldn't alternating nicotinamide treatment with a Sirt1 activator like PQQ give you everything you need?

Edited by Turnbuckle, 27 October 2016 - 06:36 PM.

[mrkosh1]

The other ingredients in the cocktail are listed on the company's website. I don't see how any of them would help get the NAD+ into the cells unmodified. However, methyl donors like B12 might be able to offset any negative production of homocycsteine.

 

My understanding is that both NAD+ and NMN are both converted to NR outside the cell and then taken inside as NR.

 

Nicotinamide is interesting because it probably has the same effects as NR except for SIRT inhibition and PARP inhibition at higher doses. If the mitophagy effects are triggered by the NAD+ increase, then I expect that they could also be triggered by NR. In the following paper, mitophagy is hindered by the inhibition of SIRT1.

 

https://www.ncbi.nlm...les/PMC4625837/

 

Personally, I don't like the idea of reducing my mitochondrial content so abruptly. For all we know, without the SIRT and other genes active, non-defective mitochondria could be removed. My personal preference would be to give my cells the NR needed for them to fuel all their processes. It seems to me that the use of NAM which inhibits all SIRTS and PARPS is a little dangerous.

 

I found another quote:

https://www.ncbi.nlm...PMC4500936/#R40

 

Reduced NADH/NAD⁺ Ratio

In either its oxidized (NAD⁺) or reduced (NADH) form, NAD is an essential substrate for multiple metabolic circuitries, including (but not limited to) glycolysis, the Krebs cycle, and oxidative phosphorylation. The exposure of cells to nutrient-free conditions causes the accumulation of NAD⁺ at the expense of NADH, promoting autophagy upon activation of histone deacetylases of the sirtuin family (Houtkooper et al., 2012). Conversely, the intracellular levels of both NAD⁺ and NADH fall upon the activation of NAD⁺-dependent enzymes such as poly(ADP-ribose) polymerase 1 (PARP1) (Gibson and Kraus, 2012). Inhibition of these enzymes (which preserves the endogenous levels of NAD) as well as the artificial supply of NAD precursors (e.g., nicotinamide, nicotinamide riboside) potently triggers autophagy upon the activation of sirtuins, whose enzymatic activity critically relies on NAD⁺ (Houtkooper et al., 2012). Thus, not only the relative abundance of NADH and NAD⁺, but also the total availability of NAD has profound autophagy-modulatory effects.

 

--

 

The above makes me think that NR should increase mitophagy in a similar manner to nicotinamide without the inhibition of other important genes.

 

[richard hnry]

This is getting confusing. What would be the best way to tear down an rebuild the most mitochondria so that we can regain our youthful energy levels?

[elfanjo]

Lol

[sthira]

This is getting confusing. What would be the best way to tear down an rebuild the most mitochondria so that we can regain our youthful energy levels?

Big question, right? And I think we have nothing yet out of labs or available at amazon. Support SENS now for a brighter future.

While await science, maybe self-experiment with calorie restriction and periodic, prolonged fasting (>3 days). Regularly scheduled, consistent fasts may trigger the body into a self-digestion program. The idea (e.g., see Valter Longo) is fasting preens, recycles, destroys, excretes weaker cells; resumption of eating (an RDA-conforming plant-based Mediterranean diet) may help to rebuild parts of those damaged tissues and organs.

Fasting tears it down; refeeding builds it up. A more efficient system with increased energy and strength has been my n=1.

[BieraK]

This is getting confusing. What would be the best way to tear down an rebuild the most mitochondria so that we can regain our youthful energy levels?

The same question I have been asking myself for some time now. Consuming Nicotinamide with PQQ Looks Better Than Consuming Nicotinamide alone, PQQ activates Sirt1
https://www.ncbi.nlm...pubmed/26275361
 

From this isolated parragraph in the main study in the "A protocol to upgrade mitochondria" thread: 

On the contrary, SIRT1 activation has been reported to induce mitochondrial biogenesis, which would result in an increase in the mitochondrial content. In these studies, treatment with either resveratrol (44) or SRT1720 (45) activated PGC-1α and thereby induced mitochondrial biogenesis, which in turn results in an increased aerobic capacity of primary cultured cells or mice. If both mitochondrial autophagy and biogenesis occur simultaneously in a cell, these seemingly contradictory effects of SIRT1 would play an important role in mitochondrial quality maintenance, because mitochondrial biogenesis coupled with active mitophagy would repopulate functional mitochondria, resulting in the restoration of a healthy population of mitochondria (46)

 

 

 

Edited by BieraK, 04 January 2017 - 11:40 AM.

[richard hnry]

I will try taking NR along with PQQ in the morning and see if it gives me improved energy.  If it truly does tear down and rebuild the mitochondria then I should know.

 

This is getting confusing. What would be the best way to tear down an rebuild the most mitochondria so that we can regain our youthful energy levels?

The same question I have been asking myself for some time now. Consuming Nicotinamide with PQQ Looks Better Than Consuming Nicotinamide alone, PQQ activates Sirt1
https://www.ncbi.nlm...pubmed/26275361
 

From this isolated parragraph in the main study in the "A protocol to upgrade mitochondria" thread: 

On the contrary, SIRT1 activation has been reported to induce mitochondrial biogenesis, which would result in an increase in the mitochondrial content. In these studies, treatment with either resveratrol (44) or SRT1720 (45) activated PGC-1α and thereby induced mitochondrial biogenesis, which in turn results in an increased aerobic capacity of primary cultured cells or mice. If both mitochondrial autophagy and biogenesis occur simultaneously in a cell, these seemingly contradictory effects of SIRT1 would play an important role in mitochondrial quality maintenance, because mitochondrial biogenesis coupled with active mitophagy would repopulate functional mitochondria, resulting in the restoration of a healthy population of mitochondria (46)

 

 

 

 

[nicklesprout]

anyone know where to get NAD in IV form?

[sunshinefrost]

i've tried benagene and NR and i'm very sensitive to both. I find that both augment my stress level (very wired)  but NR is cleaner in terms of agitation. what's wierd is I have to split 1 pill of NR in 5 portions (even more)  in order for it not to affect my sleep too much. i feel it for the rest of the day. My speech and fluid\working memory is improved all day. 

 

Does anyone know why some people respond immensely to NAD+ boosters ? 

 

 

Edited by sunshinefrost, 24 January 2017 - 01:11 AM.

[sunshinefrost]

anyone know where to get NAD in IV form?

 

i suggest to trial it in pill form before, you may be surprised. i got drastic improvemments from them. If you inject you will certainly feel the benefits right away. There may be a slight "loading phase" beforehand but it's worth the wait.