2255 replies to this topic

[Nate-2004]

Here is the link to a paper which specifically shows that Alpha Lipoic Acid can boost the levels of NAD+ and change the ratio.

 

http://www.ncbi.nlm....pubmed/22456698

RESULTS:

ALA increased the NAD(+)/NADH ratio to enhance SIRT1 activity and production in C(2)C(12) myotubes. ALA subsequently increased AMPK and ACC phosphorylation, leading to increased palmitate β-oxidation and decreased intracellular triacylglycerol accumulation in C(2)C(12) myotubes. In cells treated with nicotinamide or transfected with SIRT1 siRNA, ALA-mediated AMPK/ACC phosphorylation, intracellular triacylglycerol accumulation and palmitate β-oxidation were reduced, suggesting that SIRT1 is an upstream regulator of AMPK. ALA increased ATGL and suppressed FAS protein production in C(2)C(12) myotubes. Oral administration of ALA in diabetic mice fed on a high-fat diet and db/db mice dramatically reduced the body weight and visceral fat content.

 

I was going to respond that the study linked previously made no mention of NAD boosting and that it had a ridiculously small sample size in mice. Why are these studies using such a small sample size? Is it funding? Without access to the full text to the next one I can't see what kind of sample size they used as far as the in vivo portion is concerned. This is weak at best but a very interesting hypothesis nonetheless. It would be exciting if it turned out to be true. NR is so expensive but ALA doesn't appear to be. If this were true we wouldn't necessarily have to take so much NR (1g in recent Chromadex trials) to boost it considerably.

 

I assume we're talking about ALA because it's available whereas this other substance, beta-lapachone is not?  

 

Side thought: Considering the fact that both Nicotinamide Riboside and Alpha Lipoic Acid are available for human consumption, can we crowd fund a double blind controlled human trial to determine whether or not this is true?

 

Question: People are mentioning better results with niacin in the thread. First off I'm not sure what "results" are expected. Some people take supplements expecting some miraculous change but I would say that you can't really know what's going on in such a short period of time, even if it is proven that NAD is boosted by 30-50%. If at the very least aging is prevented or slowed, you couldn't possibly know for at least a decade. However if nacin does also boost NAD+ then what would be the difference between niacin (flush) NA and niacinamide NAA (no flush) in this context? Do both do pretty much the same thing with NAD? Does niacinamide (NAA) inhibit sirtuins or is that just nicotinamide (NAM)?

Edited by Nate-2004, 01 June 2016 - 09:07 PM.

[Skyguy2005]

 

Question: People are mentioning better results with niacin in the thread. First off I'm not sure what "results" are expected. Some people take supplements expecting some miraculous change but I would say that you can't really know what's going on in such a short period of time, even if it is proven that NAD is boosted by 30-50%. If at the very least aging is prevented or slowed, you couldn't possibly know for at least a decade. However if nacin does also boost NAD+ then what would be the difference between niacin (flush) NA and niacinamide NAA (no flush) in this context? Do both do pretty much the same thing with NAD? Does niacinamide (NAA) inhibit sirtuins or is that just nicotinamide (NAM)?

 

 

I do get strong feelings from supplements yeah it's weird I know. For example, everything I've read says Ginkgo Biloba and Resveratrol are good... and everything I've felt says the same thing. Meanwhile, everything I've read says NR>NA, but everything I've felt says the exact opposite. 

 

Nicotinamide and Niacinamide are the same thing. This (http://biochem.uiowa...nts/bogan08.pdf) says Nicotiniac Acid is a better NAD+ source than Nicotinamide in the liver. For SIRT1 Niacinamide is dubious and Niacinic Acid is just fine AFAIK. 

Edited by Skyguy2005, 01 June 2016 - 11:48 PM.

[Bryan_S]

Here is the link to a paper which specifically shows that Alpha Lipoic Acid can boost the levels of NAD+ and change the ratio.

 

http://www.ncbi.nlm....pubmed/22456698

RESULTS:

ALA increased the NAD(+)/NADH ratio to enhance SIRT1 activity and production in C(2)C(12) myotubes. ALA subsequently increased AMPK and ACC phosphorylation, leading to increased palmitate β-oxidation and decreased intracellular triacylglycerol accumulation in C(2)C(12) myotubes. In cells treated with nicotinamide or transfected with SIRT1 siRNA, ALA-mediated AMPK/ACC phosphorylation, intracellular triacylglycerol accumulation and palmitate β-oxidation were reduced, suggesting that SIRT1 is an upstream regulator of AMPK. ALA increased ATGL and suppressed FAS protein production in C(2)C(12) myotubes. Oral administration of ALA in diabetic mice fed on a high-fat diet and db/db mice dramatically reduced the body weight and visceral fat content.

 

I can see from both articles an observed increase in SIRT1 and SIRT3 proteins and a shift in the NAD(+)/NADH ratio. I'd say at this point the research is slim but suggestive. What I like is this stuff is readily available, inexpensive and can be orally administrated. I did a quick glance to see about alpha lipoic acid toxicity and again we have very slim data that will need research. I'd say keep your eye out for more articles and keep us posted. 

[mrkosh1]

Nate,

 

I'm all for LongeCity sponsoring a test to compare the effect of LA to NR and to see if the two substances synergise. The way I see it, there would need to be at least four groups -- a control, a group given a high dose of NR, a group given a high dose of R-alpha lipoic acid, and a group given a high dose of both. If the money is available, low dose groups would be ideal as well. Volunteers would need a "washout" period from other supplements for a minimum of a few days. At a minimum, NAD+ and SIRT levels should be tested before and after each dose is administered.

 

If it would take years to see the results of a therapy, I think the therapy needs to be re-worked. I personally think for us to see rapid anti-aging we will need to increase the NAD levels very high. I don't think NR or ALA can rapidly reverse aging by themselves, but they may be able to have a big impact together.

 

In my opinion, ALA is a better option than Beta Lapachone for a test because the cost of the supplement would be far less, the supplement would be far more available, and ALA has a more verifiable safety record. Now, I agree there needs to be more lifespan studies using ALA. However, it usually produces few ill effects even at higher doses. I personally would feel far more comfortable consuming R-ALA (I'd never take standard ALA which is a mix of both S and R isomers) than Beta Lapachone.

 

 

[Skyguy2005]

Nate,

 

I'm all for LongeCity sponsoring a test to compare the effect of LA to NR and to see if the two substances synergise. The way I see it, there would need to be at least four groups -- a control, a group given a high dose of NR, a group given a high dose of R-alpha lipoic acid, and a group given a high dose of both. If the money is available, low dose groups would be ideal as well. Volunteers would need a "washout" period from other supplements for a minimum of a few days. At a minimum, NAD+ and SIRT levels should be tested before and after each dose is administered.

 

If it would take years to see the results of a therapy, I think the therapy needs to be re-worked. I personally think for us to see rapid anti-aging we will need to increase the NAD levels very high. I don't think NR or ALA can rapidly reverse aging by themselves, but they may be able to have a big impact together.

 

In my opinion, ALA is a better option than Beta Lapachone for a test because the cost of the supplement would be far less, the supplement would be far more available, and ALA has a more verifiable safety record. Now, I agree there needs to be more lifespan studies using ALA. However, it usually produces few ill effects even at higher doses. I personally would feel far more comfortable consuming R-ALA (I'd never take standard ALA which is a mix of both S and R isomers) than Beta Lapachone.

 

What is the evidence for ALA in tauopathies (Alzheimers, Huntingtons, Parkinsons etc.)? That is where I always look first, as *all* of the known "goodies" (Ginkgo Biloba, Curcumin, Resveratrol, Glucosamine, Rapamycin, et al) seem to have activity there. I'm not an expert but I would put that as a *prerequisite* for being impessed by something. 

 

"C-F. Lipoic acid (LA) inhibits starvation-induced autophagy and restores AcCoA depletion and cytoplasmic proteins acetylation. Supplementation of lipoic acid, an activator of the pyruvatedehydrogenase complex (PDH) increased both cellular AcCoA (but not ATPs) levels © and cytoplasmic protein acetylation (D) in nutrient-depleted cells. Treatment with lipoic acid also abolished starvation-induced autophagy as measured by GFP-LC3 puncta (E) and LC3 lipidation (F)."

 

http://www.cell.com/...98823/mmc1.pdf 

 

Seems to say it inhibits starvation-induced autophagy. Sounds like a red flag to me. 

Edited by Skyguy2005, 02 June 2016 - 06:53 PM.

[Yajerman]

Nate,

 

I'm all for LongeCity sponsoring a test to compare the effect of LA to NR and to see if the two substances synergise. The way I see it, there would need to be at least four groups -- a control, a group given a high dose of NR, a group given a high dose of R-alpha lipoic acid, and a group given a high dose of both. If the money is available, low dose groups would be ideal as well. Volunteers would need a "washout" period from other supplements for a minimum of a few days. At a minimum, NAD+ and SIRT levels should be tested before and after each dose is administered.

 

If it would take years to see the results of a therapy, I think the therapy needs to be re-worked. I personally think for us to see rapid anti-aging we will need to increase the NAD levels very high. I don't think NR or ALA can rapidly reverse aging by themselves, but they may be able to have a big impact together.

 

In my opinion, ALA is a better option than Beta Lapachone for a test because the cost of the supplement would be far less, the supplement would be far more available, and ALA has a more verifiable safety record. Now, I agree there needs to be more lifespan studies using ALA. However, it usually produces few ill effects even at higher doses. I personally would feel far more comfortable consuming R-ALA (I'd never take standard ALA which is a mix of both S and R isomers) than Beta Lapachone.

 

I just purchased R-ALA and I have been taking Basis for a few months. I will be taking 300mg a day of R-ALA for the next few months just to see if I notice any difference. I am 43 and relatively healthy and workout daily so I doubt I will notice any significant difference. I haven't changed my dietary habits for years so if you guys want i can help out in any shape or form you guys like get blood drawn now, etc etc. let me know

[Nate-2004]

 

Nate,

 

I'm all for LongeCity sponsoring a test to compare the effect of LA to NR and to see if the two substances synergise. The way I see it, there would need to be at least four groups -- a control, a group given a high dose of NR, a group given a high dose of R-alpha lipoic acid, and a group given a high dose of both. If the money is available, low dose groups would be ideal as well. Volunteers would need a "washout" period from other supplements for a minimum of a few days. At a minimum, NAD+ and SIRT levels should be tested before and after each dose is administered.

 

If it would take years to see the results of a therapy, I think the therapy needs to be re-worked. I personally think for us to see rapid anti-aging we will need to increase the NAD levels very high. I don't think NR or ALA can rapidly reverse aging by themselves, but they may be able to have a big impact together.

 

In my opinion, ALA is a better option than Beta Lapachone for a test because the cost of the supplement would be far less, the supplement would be far more available, and ALA has a more verifiable safety record. Now, I agree there needs to be more lifespan studies using ALA. However, it usually produces few ill effects even at higher doses. I personally would feel far more comfortable consuming R-ALA (I'd never take standard ALA which is a mix of both S and R isomers) than Beta Lapachone.

 

I just purchased R-ALA and I have been taking Basis for a few months. I will be taking 300mg a day of R-ALA for the next few months just to see if I notice any difference. I am 43 and relatively healthy and workout daily so I doubt I will notice any significant difference. I haven't changed my dietary habits for years so if you guys want i can help out in any shape or form you guys like get blood drawn now, etc etc. let me know

 

 

From what I understand the body loses its capacity to produce more NAD as you age or is it that it's just producing less?  If it's losing its ability to produce more NAD then it's interesting that simply giving it materials to produce it such as NR would increase NAD production.  It would seem as though figuring out exactly why it's losing its capacity would be the key to getting your body to produce more. I'm not sure how ALA would fix the problem whatever the root cause is. It might, but it might not. This is why I think it's important to determine the root cause in the loss of production capacity before we can actually boost it to the levels of a 20 year old. Taking ALA seems like hitting buttons and seeing if anything happens which is fine, at least it's an educated guess, but an inefficient route.

 

If it's not losing its ability and rather having trouble getting ingredients so to speak, and simply giving it more ingredients (NR) is the key then all we'd have to do is take more NR.

 

Does this not make sense?

Edited by Nate-2004, 02 June 2016 - 09:28 PM.

[sthira]

Of course that makes sense, Nate. It seems to me this is what supplements generally do: push buttons. Which buttons, how intensely, how often, what are the downstream effects? All remains still mostly unknown, even the miracle of an apple's effect on metabolism is way beyond understanding. We need to solve root problems, and no study of a single substance is gonna get us there, I speculate.

[normalizing]

 

Nate,

 

I'm all for LongeCity sponsoring a test to compare the effect of LA to NR and to see if the two substances synergise. The way I see it, there would need to be at least four groups -- a control, a group given a high dose of NR, a group given a high dose of R-alpha lipoic acid, and a group given a high dose of both. If the money is available, low dose groups would be ideal as well. Volunteers would need a "washout" period from other supplements for a minimum of a few days. At a minimum, NAD+ and SIRT levels should be tested before and after each dose is administered.

 

If it would take years to see the results of a therapy, I think the therapy needs to be re-worked. I personally think for us to see rapid anti-aging we will need to increase the NAD levels very high. I don't think NR or ALA can rapidly reverse aging by themselves, but they may be able to have a big impact together.

 

In my opinion, ALA is a better option than Beta Lapachone for a test because the cost of the supplement would be far less, the supplement would be far more available, and ALA has a more verifiable safety record. Now, I agree there needs to be more lifespan studies using ALA. However, it usually produces few ill effects even at higher doses. I personally would feel far more comfortable consuming R-ALA (I'd never take standard ALA which is a mix of both S and R isomers) than Beta Lapachone.

 

What is the evidence for ALA in tauopathies (Alzheimers, Huntingtons, Parkinsons etc.)? That is where I always look first, as *all* of the known "goodies" (Ginkgo Biloba, Curcumin, Resveratrol, Glucosamine, Rapamycin, et al) seem to have activity there. I'm not an expert but I would put that as a *prerequisite* for being impessed by something. 

 

"C-F. Lipoic acid (LA) inhibits starvation-induced autophagy and restores AcCoA depletion and cytoplasmic proteins acetylation. Supplementation of lipoic acid, an activator of the pyruvatedehydrogenase complex (PDH) increased both cellular AcCoA (but not ATPs) levels © and cytoplasmic protein acetylation (D) in nutrient-depleted cells. Treatment with lipoic acid also abolished starvation-induced autophagy as measured by GFP-LC3 puncta (E) and LC3 lipidation (F)."

 

http://www.cell.com/...98823/mmc1.pdf 

 

Seems to say it inhibits starvation-induced autophagy. Sounds like a red flag to me. 

 

 

it was discussed before, it has good safety profile and long term use with a lot of proposed benefits but it happened in another thread it was another antioxidant double-edge which is hormesis based, ALL antioxidants WILL interfere with CR or exercise benefits.

[tunt01]

Lipoic acid should be viewed as an insulin mimetic. That's why it inhibits autophagy, because it stimulates protein synthesis and is antilipogenic. Take it with a meal. Half life approx 20-30 MINS

[normalizing]

i dont see insulin mimetics as pro longevity. im still waiting for the person or the thread being made where it encourage snorting/injecting INSULIN and positive data, and specified study results!

[Skyguy2005]

 

 

Nate,

 

I'm all for LongeCity sponsoring a test to compare the effect of LA to NR and to see if the two substances synergise. The way I see it, there would need to be at least four groups -- a control, a group given a high dose of NR, a group given a high dose of R-alpha lipoic acid, and a group given a high dose of both. If the money is available, low dose groups would be ideal as well. Volunteers would need a "washout" period from other supplements for a minimum of a few days. At a minimum, NAD+ and SIRT levels should be tested before and after each dose is administered.

 

If it would take years to see the results of a therapy, I think the therapy needs to be re-worked. I personally think for us to see rapid anti-aging we will need to increase the NAD levels very high. I don't think NR or ALA can rapidly reverse aging by themselves, but they may be able to have a big impact together.

 

In my opinion, ALA is a better option than Beta Lapachone for a test because the cost of the supplement would be far less, the supplement would be far more available, and ALA has a more verifiable safety record. Now, I agree there needs to be more lifespan studies using ALA. However, it usually produces few ill effects even at higher doses. I personally would feel far more comfortable consuming R-ALA (I'd never take standard ALA which is a mix of both S and R isomers) than Beta Lapachone.

 

What is the evidence for ALA in tauopathies (Alzheimers, Huntingtons, Parkinsons etc.)? That is where I always look first, as *all* of the known "goodies" (Ginkgo Biloba, Curcumin, Resveratrol, Glucosamine, Rapamycin, et al) seem to have activity there. I'm not an expert but I would put that as a *prerequisite* for being impessed by something. 

 

"C-F. Lipoic acid (LA) inhibits starvation-induced autophagy and restores AcCoA depletion and cytoplasmic proteins acetylation. Supplementation of lipoic acid, an activator of the pyruvatedehydrogenase complex (PDH) increased both cellular AcCoA (but not ATPs) levels © and cytoplasmic protein acetylation (D) in nutrient-depleted cells. Treatment with lipoic acid also abolished starvation-induced autophagy as measured by GFP-LC3 puncta (E) and LC3 lipidation (F)."

 

http://www.cell.com/...98823/mmc1.pdf 

 

Seems to say it inhibits starvation-induced autophagy. Sounds like a red flag to me. 

 

 

it was discussed before, it has good safety profile and long term use with a lot of proposed benefits but it happened in another thread it was another antioxidant double-edge which is hormesis based, ALL antioxidants WILL interfere with CR or exercise benefits.

 

 

Many herbal supplements activate autophagy and are also classed as "antioxidants".  

[Female Scientist]

What do you guys know about this new study, just posted 6/2/16? Not sure if NR is a component of the supplement so my apologies if this is not the right thread to post, but I assume someone can comment/point us in the right direction?

 

From the ScienceDaily summary:

 

Fountain of youth? Dietary supplement may prevent and reverse severe damage to aging brain, research suggests.  A dietary supplement containing a blend of thirty vitamins and minerals--all natural ingredients widely available in health food stores--has shown remarkable anti-aging properties that can prevent and even reverse massive brain cell loss, according to new research. It's a mixture scientists believe could someday slow the progress of catastrophic neurological diseases such as Alzheimer's, ALS and Parkinson's.

 

Citation here:

http://onlinelibrary...2/em.22019/full

[APBT]

What do you guys know about this new study, just posted 6/2/16? Not sure if NR is a component of the supplement so my apologies if this is not the right thread to post, but I assume someone can comment/point us in the right direction?

 

From the ScienceDaily summary:

 

Fountain of youth? Dietary supplement may prevent and reverse severe damage to aging brain, research suggests.  A dietary supplement containing a blend of thirty vitamins and minerals--all natural ingredients widely available in health food stores--has shown remarkable anti-aging properties that can prevent and even reverse massive brain cell loss, according to new research. It's a mixture scientists believe could someday slow the progress of catastrophic neurological diseases such as Alzheimer's, ALS and Parkinson's.

 

Citation here:

http://onlinelibrary...2/em.22019/full

 

 

See this thread:  http://www.longecity...hat-a-surprise/

[brighty]

Hi,

 

Are there any conflicts or synergy between Nicotinamide Riboside and Resveratrol / Curcumin? I am currently taking Elysium Basis (which has 250mg of Nicotinamide Riboside) along with 500 mg of Resveratrol together in the morning. I may even add Curcumin to my regimen. I am starting to wonder whether I should move my Resveratrol and Curcumin (potentially) doses to the afternoon. Should I take them  together or separately? Any feedback would be appreciated.

 

Thanks

 

[Bryan_S]

ChromaDex Announces $5.25 Million Registered Direct Offering

 

https://globenewswir...t-Offering.html

 

This doesn't affect the users directly but the stock price is expected to plummet to the announced figure.

 

"The Company agreed to sell 1,117,022 shares of its common stock at a per share price of $4.70, for gross proceeds of approximately $5.25 million. All of the shares of common stock were offered pursuant to an effective shelf registration statement. There were no warrants associated with this transaction.

 

Proceeds from the transaction will be used to pay off the Company’s existing debt facility. The amount of principal currently outstanding on the Debt facility is $4,554,659.04, and the total payoff amount including accrued interest and other payments due is approximately $4,858,000. Upon final payment, the facility will terminate." 

 

Guess they feel they can offset their debt considerably.

[Bryan_S]

Hi,

 

Are there any conflicts or synergy between Nicotinamide Riboside and Resveratrol / Curcumin? I am currently taking Elysium Basis (which has 250mg of Nicotinamide Riboside) along with 500 mg of Resveratrol together in the morning. I may even add Curcumin to my regimen. I am starting to wonder whether I should move my Resveratrol and Curcumin (potentially) doses to the afternoon. Should I take them  together or separately? Any feedback would be appreciated.

 

Thanks

 

Don't know about Curcumin but to be honest, it hasn't been a focus of mine. "Equine Supplement to Include ChromaDex’s pTeroGold Pterostilbene-Curcumin Hybrid Ingredient" So ChromaDex thinks its synergistic with Pterostilbene but I haven't seen a direct link to infer this. Pterostilbene is a more bioactive version of Resveratrol. Both of which (Pterostilbene/Resveratrol) should be synergistic with (NR).

Edited by Bryan_S, 06 June 2016 - 11:15 PM.

[mrkosh1]

I've been thinking deeply about whether or not I should purchase some NR or Alpha Lipoic Acid.

 

My conclusion is that neither one of them seems to offer "extreme" levels of anti-aging effects. They both provide significant health benefits, but I'm unsure if either one will literally "turn back the clock" significantly in a fairly short duration of time (months instead of years). However, I think there is a chance the two could be synergistic. PGC-1a is activated very strongly by Alpha Lipoic Acid and can increase the amount of SIRT1 protein by six fold! NR doesn't increase the amount of protein by any measurable amount, but simply provides NAD+ to activate it.

 

So if we can produce six times the SIRT1 protein and activate all of it, I think that could yield a potent anti-aging effect.

 

In my opinion, the NAD+, telomerase, and SIRT boosting properties of ALA and NR needs to be tested, ASAP.

 

[Bryan_S]

I've been thinking deeply about whether or not I should purchase some NR or Alpha Lipoic Acid.

 

My conclusion is that neither one of them seems to offer "extreme" levels of anti-aging effects. They both provide significant health benefits, but I'm unsure if either one will literally "turn back the clock" significantly in a fairly short duration of time (months instead of years). However, I think there is a chance the two could be synergistic. PGC-1a is activated very strongly by Alpha Lipoic Acid and can increase the amount of SIRT1 protein by six fold! NR doesn't increase the amount of protein by any measurable amount, but simply provides NAD+ to activate it.

 

So if we can produce six times the SIRT1 protein and activate all of it, I think that could yield a potent anti-aging effect.

 

In my opinion, the NAD+, telomerase, and SIRT boosting properties of ALA and NR needs to be tested, ASAP.

 

I hadn't read that do we have a study link?

[Harkijn]

 

I've been thinking deeply about whether or not I should purchase some NR or Alpha Lipoic Acid.

 

My conclusion is that neither one of them seems to offer "extreme" levels of anti-aging effects. They both provide significant health benefits, but I'm unsure if either one will literally "turn back the clock" significantly in a fairly short duration of time (months instead of years). However, I think there is a chance the two could be synergistic. PGC-1a is activated very strongly by Alpha Lipoic Acid and can increase the amount of SIRT1 protein by six fold! NR doesn't increase the amount of protein by any measurable amount, but simply provides NAD+ to activate it.

 

So if we can produce six times the SIRT1 protein and activate all of it, I think that could yield a potent anti-aging effect.

 

In my opinion, the NAD+, telomerase, and SIRT boosting properties of ALA and NR needs to be tested, ASAP.

 

I hadn't read that do we have a study link?

 

This connection is intriguing. The very first time I read something about nicotinamide was in connection with ALA:

 

http://www.ncbi.nlm....pubmed/21507065

[albedo]

Following the European NUGO project for personalized nutrition and health span, e.g. see here, I found this interesting poster presentation (p. 106) on metabolic flexibility at different NR concentrations and prolonged use. Not sure this has been reported here and/or published.

 

Effects of different dietary nicotinamide riboside concentrations on physiological phenotype in mice

 

"Metabolic flexibility is characterized by the ability to rapidly switch between carbohydrate and fat oxidation. NAD+ plays a crucial role in both carbohydrate and fat oxidation as an electron donor or a coenzyme. NAD+ can be converted from different precursors, one of which is nicotinamide riboside (NR). Previous studies have shown that NR supplementation could promote cellular metabolic state. However, whether NR affects metabolic flexibility is still unclear. Our objective was to examine the effects of different dietary NR concentrations on metabolic flexibility in mice fed a high fat diet. Male C57BL/6JRcc mice arrived at 9 weeks old. After 4 weeks of adaptation on a low fat diet (en10%, 30 mg/kg NR), mice were stratified into 5 groups (n=12 per group). Each group was ad libitum fed for 15 weeks with a high fat diet (en40%) containing 0.10% L-tryptophan and either 5, 15, 30, 180 or 900 mg/kg NR. Body weight, lean mass, fat mass and feed intake were measured weekly. After 10 and 14 weeks, indirect calorimetry (InCa) was performed, including a fast-refeeding challenge. Inca data were used to calculate the delta respiratory exchange ratio (RER) when switching from fatty acid to carbohydrate oxidation (ΔRERFAO-CHO) and switching from carbohydrate to fatty acid oxidation (ΔRERCHO-FAO), which may reflect metabolic flexibility. In addition, energy expenditure (EE) and activity were measured during InCa. After 15 weeks, mice were sacrificed and blood glucose, and serum triglycerides (TG), non-esterified fatty acid (NEFA), insulin, leptin, adiponectin were analysed. Results showed that ΔRERFAO-CHO was greater in the 30 mg/kg NR group than in the 5 mg/kg, 15 mg/kg or 900 mg/kg NR groups at week 14. Also, the ΔRERCHO-FAO was greater in 30 mg/kg than that in 5 mg/kg group. At week 10, however, these differences were not visible yet. EE and activity did not differ at week 10 nor week 14. Similarly, we did not find differences in body weight, lean mass, fat mass and cumulative feed intake over a 15-week period. Although there were no differences in serum insulin, leptin, adiponectin, adiponectin/leptin ratio, TG, NEFA or blood glucose, we found significant correlations between adiponectin/leptin ratio and ΔRERFAO-CHO or ΔRERCHO-FAO. Current results suggest that 30 mg/kg of dietary NR intervention can lead to the greatest metabolic flexibility among the five NR treatments, which cannot be explained by energy expenditure and activities. Notably, this benefit on metabolic flexibility occurs after prolonged NR intervention. The association of metabolic flexibility with serum adiponectin/leptin ratio suggests involvement of adipose tissue in metabolic flexibility." (red mine)

[Tom Andre F. (ex shinobi)]

 

 

I've been thinking deeply about whether or not I should purchase some NR or Alpha Lipoic Acid.

 

My conclusion is that neither one of them seems to offer "extreme" levels of anti-aging effects. They both provide significant health benefits, but I'm unsure if either one will literally "turn back the clock" significantly in a fairly short duration of time (months instead of years). However, I think there is a chance the two could be synergistic. PGC-1a is activated very strongly by Alpha Lipoic Acid and can increase the amount of SIRT1 protein by six fold! NR doesn't increase the amount of protein by any measurable amount, but simply provides NAD+ to activate it.

 

So if we can produce six times the SIRT1 protein and activate all of it, I think that could yield a potent anti-aging effect.

 

In my opinion, the NAD+, telomerase, and SIRT boosting properties of ALA and NR needs to be tested, ASAP.

 

I hadn't read that do we have a study link?

 

This connection is intriguing. The very first time I read something about nicotinamide was in connection with ALA:

 

http://www.ncbi.nlm....pubmed/21507065

 

You really should forget about it... ALA is produced naturally by the body as a strong master antioxidant. However, If you supplement yourself with it you will actually decrease your own production so go to the opposite effect. In mice the supplementation decrease lifespan significantly : http://www.ncbi.nlm....pubmed/22785389

 

There is also others studies I read in the past that show its negative part..

 

[normalizing]

"These results indicate that alpha-lipoic acid improves memory and reverses indices of oxidative stress in extremely old SAMP8 mice, but decreases lifespan"

 

what the hell is this, how can it improve memory and REVERSE OXIDATIVE STRESS but decrease lifespan? wow just strange

[Smedvick]

"These results indicate that alpha-lipoic acid improves memory and reverses indices of oxidative stress in extremely old SAMP8 mice, but decreases lifespan"

 

what the hell is this, how can it improve memory and REVERSE OXIDATIVE STRESS but decrease lifespan? wow just strange

It gets weirder too as it ends with "These findings are similar to studies using other types of antioxidants."  So antioxidants in general decrease lifespan?

[normalizing]

but enhanced quality of life is better than longer life with still no possibility of curing it

Edited by normalizing, 08 June 2016 - 02:19 AM.

[stefan_001]

 

Hi,

 

Are there any conflicts or synergy between Nicotinamide Riboside and Resveratrol / Curcumin? I am currently taking Elysium Basis (which has 250mg of Nicotinamide Riboside) along with 500 mg of Resveratrol together in the morning. I may even add Curcumin to my regimen. I am starting to wonder whether I should move my Resveratrol and Curcumin (potentially) doses to the afternoon. Should I take them  together or separately? Any feedback would be appreciated.

 

Thanks

 

Don't know about Curcumin but to be honest, it hasn't been a focus of mine. "Equine Supplement to Include ChromaDex’s pTeroGold Pterostilbene-Curcumin Hybrid Ingredient" So ChromaDex thinks its synergistic with Pterostilbene but I haven't seen a direct link to infer this. Pterostilbene is a more bioactive version of Resveratrol. Both of which (Pterostilbene/Resveratrol) should be synergistic with (NR).

 

 

I just bought some Curcumon for my mom. She has osteoathritis. She is also on Ptero and NR, lets see what she says after a month or so - ofcourse that is only n=1 but still. Here a recent study on the OA:

http://www.ncbi.nlm....pubmed/27260322

 

 

[normalizing]

ive been experimenting with NR for a month on and off now, i dont get it, i use quite high dose of 500mg and there is no a single noticeable effect. i tried it today again for fatigue, but usually even simple coconut water helps a bit with fatigue and this praised crap doesnt!? wow

 

please post experience comments here:

http://www.longecity.org/forum/topic/69729-nicotinamide-riboside-nrniagen-personal-experience-thread/page-25

Edited by Bryan_S, 09 June 2016 - 02:29 AM.
wrong thread

[Nate-2004]

What effect are you people expecting? It's not LSD. First of all how old are you? Is NAD even a problem yet? Second of all, how do you "feel the effect" of activated sirtuins getting plenty of the NAD they're dependent upon? I don't even know what it feels like.

 

I can say that I feel something quite different but given my stack I'm not sure which one it is. I'm planning to drop different things soon once I've been taking them long enough to figure out which one it is. It could be the honokiol, it could be the NR, it could be the pterostilbene/resveratrol, it could be the C60OO, it could be the L-theanine I take at night giving me incredible sleep quality, it could be the level of vitamin D, it could be my exercise frequency, it could be my diet, it could be the accumulated effect of eating an obnoxious amount of probiotics over 1.5 years, it could be something that has nothing to do with anything I'm taking or doing. It could be holistic in that everything I'm doing is contributing in some way. I somewhat suspect the recent memory/cognition boost is coming from one of the four things I just mentioned. NR could be helping the honokiol in some way. Or what if it's all those things combined with coffee? Fuck if I know. Whatever it is, it's new and I've never felt this way. 

 

What I do feel is an outrageous amount of energy, quick witted thinking and instant recall of names and things I used to get stuck on and frustrated, and its in such a way that's shocking to me. Alcohol isn't making me that drunk anymore and its effects quickly dissipate. Whatever the case, this is one long, strong placebo effect if that's what it is.  I wanna find out which one it is but I'm enjoying the fuck out of whatever this is and afraid to give up any one of those things to find out.  I'll be forced to soon though because I can't afford NR, gonna run out in the next month so when that goes, we'll see what happens.

Edited by Nate-2004, 09 June 2016 - 02:28 AM.

[tunt01]

It could be the honokiol, it could be the NR, it could be the pterostilbene/resveratrol, 

 

 

Honokiol activates mitochondrial SIRT3. [1]   SIRT3 uses NAD+ (NR) for its activity.

 

I take 125 mg NR, 200 mg Honokiol in AM upon wake.  No food until after noon.  It seems to work pretty well.  I am not bouncing off the walls with energy, but I wouldn't want that anyway.  That would be metabolically unnatural.

 

 

 

 

 

[1]  Pillai, V., Samant, S., Sundaresan, N., Raghuraman, H., Kim, G., & Bonner, M. et al. (2015). Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nature Communications, 6, 6656. doi:10.1038/ncomms7656

[Nate-2004]

 

It could be the honokiol, it could be the NR, it could be the pterostilbene/resveratrol, 

 

 

Honokiol activates mitochondrial SIRT3. [1]   SIRT3 uses NAD+ (NR) for its activity.

 

I take 125 mg NR, 200 mg Honokiol in AM upon wake.  No food until after noon.  It seems to work pretty well.  I am not bouncing off the walls with energy, but I wouldn't want that anyway.  That would be metabolically unnatural.

 

 

 

 

 

[1]  Pillai, V., Samant, S., Sundaresan, N., Raghuraman, H., Kim, G., & Bonner, M. et al. (2015). Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nature Communications, 6, 6656. doi:10.1038/ncomms7656

 

 

I'm taking 300mg NR and 400mg honokiol twice a day right now. I'd read that the honokiol acts on specific GABAa receptors. I have essential tremor and GABA is strongly related to this neurodegenerative movement disorder. My hope is that it helps and so far it seems to have some effect but I'm not counting my chickens just yet (not literal chickens).

 

The "bouncing off the walls with energy" was just a relative before and after comparison and an expression, not meant to be literal.