42 replies to this topic

[Zaul]

 

 

Highlights

 

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Mitochondrial myopathy patients have NAD+ deficiency in muscle and blood

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Niacin is an efficient NAD+ booster in humans

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Niacin improves muscle strength and fatty liver in mitochondrial myopathy

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Niacin boosts muscle mitochondrial biogenesis and respiratory chain activity in humans

 

 

 

Summary

NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open. Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750–1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.

Graphical Abstract

 

 

https://www.scienced...30190X?via=ihub

 

[Fafner55]

Interesting that Brenner is also an author.

[able]

"Blood NAD+ increased in all subjects, up to 8-fold"

 

 

 

Whoa!  Up to 8x?  Over 10 months? Guess that was just one person, but makes the Nuchido claim of 340% increase for one person over a few weeks kinda weak.

 

Anyone have access to that?

Edited by able, 08 May 2020 - 03:02 AM.

[Zaul]

[Fafner55]

While niacin significantly lowers of LDL and raises of HDL, large clinical studies show that 1 to 3 g / day is associated with a 10% increase in all-cause mortality.

1. “Niacin - Fact Sheet for Health Professionals” https://ods.od.nih.g...thProfessional/
2. “Supplemental Vitamins and Minerals for CVD Prevention and Treatment” (2018) https://www.scienced...735109718345601

 

[Linux]

 

While niacin significantly lowers of LDL and raises of HDL, large clinical studies show that 1 to 3 g / day is associated with a 10% increase in all-cause mortality.

1. “Niacin - Fact Sheet for Health Professionals” https://ods.od.nih.g...thProfessional/
2. “Supplemental Vitamins and Minerals for CVD Prevention and Treatment” (2018) https://www.scienced...735109718345601

 

 

Increased mortality was ONLY when given together with a statin. The monotherapy niacin studies for lipid lowering did not report any increased mortality.

 

"A 2018 review of three randomized controlled trials with 29,195 patients found that all-cause mortality increased by 10% more in those who took 1 to 3 g/day extended release nicotinic acid in addition to a statin medication than patients taking the statin alone".

[Zaul]

For anyone interested, it's available now.

 

https://sci-hub.tw/h...30190X?via=ihub

[MikeDC]

Niacin is better than NAM because Niacin doesn’t inhibit NAD+ consuming processes. But niacin reduces insulin sensitivity. It also doesn’t have the anti-aging and anti inflammatory effects that NR has. If you can’t afford NR take some Niacin.

[Turnbuckle]

 

While niacin significantly lowers of LDL and raises of HDL, large clinical studies show that 1 to 3 g / day is associated with a 10% increase in all-cause mortality.

1. “Niacin - Fact Sheet for Health Professionals” https://ods.od.nih.g...thProfessional/
2. “Supplemental Vitamins and Minerals for CVD Prevention and Treatment” (2018) https://www.scienced...735109718345601

 

 

 

Your first link shows the opposite, nearly a decade after the study ended--

 

In one large clinical trial from the 1970s, 8,341 participants aged 30 to 64 years who had had one or more heart attacks were randomized to take one of five lipid-lowering medications, including 3,000 mg/day nicotinic acid, or a placebo for an average of 6.2 years [27]. Those taking nicotinic acid lowered their serum cholesterol levels by an average of 9.9% and triglyceride levels by 26.1% over 5 years of treatment. During 5 to 8.5 years of treatment, these participants had significantly fewer nonfatal myocardial infarctions but more cardiac arrhythmias than those in the placebo group. Their overall rates of mortality and cause-specific mortality, including from coronary heart disease, did not decline. But 9 years after the study ended, participants who had taken the nicotinic acid experienced significantly fewer (11%) deaths from all causes than those who had taken the placebo

 

[Fredrik]

Niacin/nicotinic acid is most certainly a proven and efficacious NAD+ precursor that doesn´t inhibit SIRT1 as niacinamide/nicotinamide does. In this study niacin increased blood levels of NAD+ 8-fold in humans and muscle strength and mitochondrial biogenesis increased in all subjects.

 

We know that NR and niacin both increase NAD+ in human whole blood when taken orally (swallowed) in pill form and we´re still awaiting confirmation that NMN can do the same in human subjects when taken orally (probably, since NMN IS NR, just with a phosphate group attached to it).

 

"NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open.

 

Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients.

 

We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.govNCT03973203) for patients and their matched controls for 10 or 4 months, respectively.

 

Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%.

 

Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy."

 

https://www.ncbi.nlm...pubmed/32386566

Edited by Fredrik, 18 May 2020 - 09:11 PM.

[SearchHorizon]

This is a significant result. The average plasma decline of NAD+ from the age 25 to 50 is about 75% (if I remember correctly). The 10 month NA administration brings it back to that level and beyond. This is as good as possible, using 1 gm/day.  

 

If you can develop tolerance against NA flushing, this pretty much "closes the book" on the quest for restoring NAD+.  

 

 

 

 

 

[MikeDC]

Niacin is a better NAD+ precursor than Nicotinamide. But niacin can cause insulin resistance. NR/NMN does not cause insulin resistance and have much better anti aging effects.

[Zaul]

Niacin is a better NAD+ precursor than Nicotinamide. But niacin can cause insulin resistance. NR/NMN does not cause insulin resistance and have much better anti aging effects.

 

It does that (only?) if you keep consuming carbs during the 4 hours (2-6 hr) FFA rebound window. Ideally you should be fasting in those 4 hours  or at the very least don't eat something with carbs. 

 

https://suppversity....-part-v-of.html

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Edited by Nigeria Custom Officer, 07 June 2020 - 12:40 PM.

[Engadin]

.

 

 

 

O P E N   A C C E S S   F U L L   T E X T (.PDF) of "Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy" @ Cell Metabolism

 

 

 

 

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[BieraK]

It does that (only?) if you keep consuming carbs during the 4 hours (2-6 hr) FFA rebound window. Ideally you should be fasting in those 4 hours or at the very least don't eat something with carbs.

https://suppversity....-part-v-of.html

Or maybe take it at night? Niacin promotes deep sleep. If combined with a 12-hour restricted feeding window, one could reap even greater benefit from it.

An interesting experiment would be to consume Niacin + Niacinamide + Ribose + TMG during the day.
100 mg Niacin
100 mg Niacinamide
250 mg Ribose
250 mg TMG
Even fewer amounts of NAM and / or Na could be used, like 50 mg.
The important thing is to maintain the proper amount of methyl donors and in case the Turnbuckle hypothesis is correct, dosing an equal or greater amount of Ribose per b3 derivative.

I have started reading Abram Hoffer's book on Niacin. That guy was an expert using Niacin, much can be learned from him.

The only problem that I consider exists with Niacin, is the feeding care that must be carried out after the FFA rebound occurs, it is supposed that no carbohydrate should be consumed there. Perhaps in lower doses during the day that is not a problem.

[Harkijn]

Sorry if I state the obvious but in case you missed it: NA raised in NAD in patients with low NAD. NA did nothing in the healthy control group. I quote:

 

In the healthy subjects, niacin did not increase muscle NAD+ , despite the 5-fold increase in the blood. These results suggest that in healthy muscle the NAD+ amounts are close to the homeostatic maximum.

 

 

 

 

[BieraK]

Sorry if I state the obvious but in case you missed it: NA raised in NAD in patients with low NAD. NA did nothing in the healthy control group. I quote:

In the healthy subjects, niacin did not increase muscle NAD+ , despite the 5-fold increase in the blood. These results suggest that in healthy muscle the NAD+ amounts are close to the homeostatic maximum.

Yes, but it increases blood NAD+ in both groups

[Fredrik]

Yes, but it increases blood NAD+ in both groups

 

How is increasing blood NAD+ levels beneficial? What is that supposed to do?

 

I´m more interested in tissue levels of NAD+, not whole blood levels.

[Harkijn]

How is increasing blood NAD+ levels beneficial? What is that supposed to do?

 

I´m more interested in tissue levels of NAD+, not whole blood levels.

 

 

Exactly my point. For healthy people the research does not provide any particular basis for taking Niacin, but who knows what future studies might bring.

That said  NA did surprisingly well for MM patients in this very small study. I hope that this proof-of -principle will get a speedy sequel and that MM patients get to hear about these results soon so they can try out for themselves.

[MikeDC]

Whole blood NAD+ is just a convenient way to measure the effects of supplementation of NAD+ precursors. We obviously can’t cut off human tissues to measure NAD+.

[Fredrik]

Whole blood NAD+ is just a convenient way to measure the effects of supplementation of NAD+ precursors. We obviously can’t cut off human tissues to measure NAD+.

 

Convenient but not very illustrative. We obviously can´t draw any conclusions on tissue levels of NAD+ by just looking at whole blood.

 

NR for example increases whole blood NAD+ (just like cheap niacin) but fails to increase muscle NAD+ in humans.

Edited by Fredrik, 13 June 2020 - 03:58 PM.

[MikeDC]

Convenient but not very illustrative. We obviously can´t draw any conclusions on tissue levels of NAD+ by just looking at whole blood.

NR for example increases whole blood NAD+ (just like cheap niacin) but fails to increase muscle NAD+ in humans.

Even NAD+ from tissues is not a good representation of effectiveness. We need clinical trials to measure the effectiveness for humans based on clinically observable data.

[Fredrik]

Even NAD+ from tissues is not a good representation of effectiveness. We need clinical trials to measure the effectiveness for humans based on clinically observable data.

 

There are 10 human clinical trials on NR that show no results at all on a panel of metabolic markers and no increase in function. How many human clinical trials showing no efficacy of NR do you need?

 

NR in humans caused a small decrease in liver fat at very high doses and a reduction in certain cytokines but no effects whatsoever on the most important markers of longevity : glucose metabolism, insulin, weight, aerobic capacity or fat oxidation. 

Edited by Fredrik, 14 June 2020 - 05:29 AM.

[MikeDC]

Remember both NAM and Niacin increases glucose.

[MikeDC]

https://pubmed.ncbi....ge=2&from_pos=1

To gain benefits for muscle, exercise is needed. Sinclair’s NMN study on mice showed benefits when mice exercised during NMN supplementation.
https://pubmed.ncbi....ge=2&from_pos=1

To gain benefits for muscle, exercise is needed. Sinclair’s NMN study on mice showed benefits when mice exercised during NMN supplementation.

[Fredrik]

Remember both NAM and Niacin increases glucose.

 

Not if you keep the dose of nicotinic acid below 500 mg, as shown in Parkinson´s disease trials.

Edited by Fredrik, 15 June 2020 - 04:42 PM.

[able]

To gain benefits for muscle, exercise is needed. Sinclair’s NMN study on mice showed benefits when mice exercised during NMN supplementation.

 

Not true. They showed benefit from NMN supplementation alone.  They showed MORE benefit with exercise, which is expected.

[JimWoodall]

Any idea if this is slow release niacin or regular? I can't imagine taking up to a gram of normal niacin per day...

[Fafner55]

Any idea if this is slow release niacin or regular? I can't imagine taking up to a gram of normal niacin per day...

 

It is possible to build up tolerance to niacin. Between 2009 and 2013 I increased my dose from 500 mg to 2000 mg in steps of 500 mg. At first, 500 mg caused intense flushing,but later I had no problem tolerating 2000 mg. 

 

I stopped taking niacin because in combination with 10 mg Crestor it pushed my LDL too low (mid 50's) and there were indications that it lowered SIRT1 expression.

 

More recently, it was shown that lowering cholesterol in the absence of risk factors (dyslipidemia, diabetes, hypertension, smoking, obesity, inactivity) increased all cause mortality.  "Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Recommendation Statement" (2017) https://www.aafp.org...7/0115/od1.html

Edited by Fafner55, 16 June 2020 - 09:59 PM.

[pamojja]

Any idea if this is slow release niacin or regular? I can't imagine taking up to a gram of normal niacin per day...

 

It is possible to build up tolerance to niacin. Between 2009 and 2013 I increased my dose from 500 mg to 2000 mg in steps of 500 mg. At first, 500 mg caused intense flushing,but later I had no problem tolerating 2000 mg.

 

Slow release isn't recommended, since it is harsher to the liver. I started with 150mg and every few days increased by ~50mg. And in short time was at 3 gram. Actually take 6g niacin every second day, to spare my liver even further. Rarely experience a very mild flush only. 500mg increases would been overwhelmingly be too much me.

Edited by pamojja, 17 June 2020 - 10:32 AM.