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Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy

pattismith

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Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy

Cell Metabolism, Volume 32, Issue 1, 7 July 2020, Pages 144

Of Mice and Men: NAD+ Boosting with Niacin Provides Hope for Mitochondrial Myopathy Patients

https://www.sciencedirect.com/science/article/abs/pii/S155041312030190X

Highlights


Mitochondrial myopathy patients have NAD+ deficiency in muscle and blood

Niacin is an efficient NAD+ booster in humans

Niacin improves muscle strength and fatty liver in mitochondrial myopathy

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.
 

Pyrrhus

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Since the summary is not so clear, here's what the paper says about the study subjects and dosages:
Five patients with variable disease duration were carefully confirmed to manifest a pure mitochondrial myopathy, with [progressive external ophthalmoplegia], ptosis, muscle weakness, and exercise intolerance. They all carried either heteroplasmic single or multiple mtDNA deletions in their muscle.
...
Two sex- and age-matched healthy controls were recruited for each patient.
...
All the subjects were supplemented with a slowly increasing dose of niacin, from 250 mg/day up to 750 or 1,000 mg/day for 4 months, and we continued the follow-up of treatment effect up to 10 months in patients.

So, according to this paper, if you have low NAD+ due to a genetic mitochondrial problem, all you need in order to boost NAD+ is vitamin B3 (niacin). Although the doses used are quite high. (The recommended dietary allowance (RDA) for niacin is 16 mg per day for men and 14 mg per day for women.) And the number of study subjects is quite low.
 

pattismith

Senior Member
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3,931
Since the summary is not so clear, here's what the paper says about the study subjects and dosages:


So, according to this paper, if you have low NAD+ due to a genetic mitochondrial problem, all you need in order to boost NAD+ is vitamin B3 (niacin). Although the doses used are quite high. (The recommended dietary allowance (RDA) for niacin is 16 mg per day for men and 14 mg per day for women.) And the number of study subjects is quite low.

I never tried high dose Niacin, but didn't get sucess from Nicotinamide up to 1500 mg per day.

Now since I started high dose Nicotinamide Riboside, together with Prenisolone (and inositol and caffeine), my muscles improved greatly, and my body shape too.

I think my disease may be related to Sjogren myopathy/neuropathy, but my husband who has post chemotherapy neuropathy + muscle wasting is now doing greatly with Nicotinamide Riboside + B12 injections + caffeine (from guarana).

Boosting NAD+ also gives hope in kidney diseases.
 

Pyrrhus

Senior Member
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I never tried high dose Niacin, but didn't get sucess from Nicotinamide up to 1500 mg per day.

Now since I started high dose Nicotinamide Riboside, together with Prenisolone (and inositol and caffeine), my muscles improved greatly, and my body shape too.

I think my disease may be related to Sjogren myopathy/neuropathy, but my husband who has post chemotherapy neuropathy + muscle wasting is now doing greatly with Nicotinamide Riboside + B12 injections + caffeine (from guarana).

So you've noticed a difference between the two popular forms of niacin? (nicotinamide vs nicotinamide riboside)

I just checked my B complex and it contains two forms of niacin, one of them called "inositol hexanicotinic acid". I will have to learn more about that one.
 
Last edited:

WantedAlive

Senior Member
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158
In the context of mitochondrial myopathy, NAD+ is involved in Complex I in the ETC. According to Fisher's research it's Complex V that is impaired, with Complex I-IV upregulated perhaps to try to maintain a leaking proton pool, or maybe to produce more ROS as an ongoing immune response. So would more NAD+ help ME/CFS? With Complex V impaired, I would've thought that boosting Complexes I-IV might help energy output but at a cost of increased ROS and potentially longer term damage, possibly at the root of the cell danger response hypothesis.

A really interesting publication 'Feeding mitochondria: Potential role of nutritional components to improve critical illness convalescence', lists Vitamin B1, B2, B3, B5, B7, B12, Zinc, Selenium, Creatine, Caffeine, CoQ10, Vitamin E, Taurine, Melatonin and Nitrate all as nutritional cofactors aiding ETC Complexes I-IV, illustrated below. What is interesting here is that most PWME report finding benefit with these very supplements, or at least they find temporary benefit until they stop working as has been my experience. Supplementing BCAA/EAA/AA for catabolic fueling of the TCA I guess achieves the same result but at least should help the nitrogen balance and preserve some loss of muscle.


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Carnitine deficiency is an interesting one, but not one I've encountered being highly beneficial in PWME. I find Acetyl-Carnitine helps a little but nothing significant. The publication states carnitine supplementation appeared to improve outcome in sepsis, and carnitine deficiency seemed prevalent in chronic critical illness.

If only we could find a supplement to help preserve mitochondrial membrane potential, I can't help but think from Fisher's study that this is a significant issue.
 

pattismith

Senior Member
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3,931
So you've noticed a difference between the two popular forms of niacin? (nicotinamide vs nicotinamide riboside)

I just checked my B complex and it contains two forms of niacin, one of them called "inositol hexanicotinic acid". I will have to learn more about that one.

Yes I noticed a dramatic difference for me between N and NR.
@Learner1 had a difference experience and found NR unhelpful, only NMN did the job for her (Nicotinamide MonoNucleotide) .

Here what a doc is saying in 2010 about the Inositol Hexanicotinic Acid you are taking (the doc advises B3 for cardiovascular health in this article)


Ask the doctor: Is no-flush niacin as effective as other kinds of niacin?

Published: March, 2010

Q. I tried taking niacin to increase my HDL but didn't like the flushing it caused. A friend told me about no-flush niacin, which works like a charm. Why not tell your readers about it?

A. When you say no-flush niacin works like a charm, I assume you mean it doesn't cause any flushing. What you might not know is that it isn't doing your HDL any good.

Niacin, also known as vitamin B3, comes in two forms — nicotinic acid and nicotinamide. Both boost protective HDL and lower harmful LDL and triglycerides. Most people who take the high doses of standard, immediate-release niacin that are needed to improve HDL experience a feeling of flushing or itching, usually in the face. It starts within 30 minutes of taking the medication, and lasts for an hour or so.

No-flush niacin doesn't contain either nicotinic acid or nicotinamide. Instead, it contains inositol hexaniacinate. In theory, the body should slowly convert this into nicotinic acid. In reality, it doesn't. An excellent study by researchers at the University of Washington School of Medicine showed that taking no-flush niacin generates virtually no free nicotinic acid, and has little or no effect on HDL. No-flush niacin lives up to the no-flush part of its name because it isn't providing the body with any niacin.

I also recommend staying away from extended-release niacin. Instead of delivering a big bolus of niacin, it generates a lower, steady dose of the medication for hours. Although this eases flushing, it keeps blood levels of niacin high all day. The liver never gets a break from processing niacin, which has led to cases of severe liver damage.

The newest niacin is intermediate-release niacin. It is currently a prescription-only medication, sold as Niaspan. It delivers niacin slower than the fast-acting types, but is washed out of the body after 12 hours or so, giving the liver a break. The slower release, combined with taking it at bedtime, helps minimize flushing, or at least the experience of it.

— Thomas Lee, M.D.
Editor in chief, Harvard Heart Letter
 

Learner1

Senior Member
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The newest niacin is intermediate-release niacin. It is currently a prescription-only medication, sold as Niaspan. It delivers niacin slower than the fast-acting types, but is washed out of the body after 12 hours or so, giving the liver a break. The slower release, combined with taking it at bedtime, helps minimize flushing, or at least the experience of it.
Of course it's prescription-only. Sounds like Thomas Lee did a good job of reading their marketing literature. Could he be getting a kickback to promote it in a Harvard publication? Perhaps consulting some other nonbiased sources might be wise...;)
 

Pyrrhus

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U.S., Earth
Yes I noticed a dramatic difference for me between N and NR.
@Learner1 had a difference experience and found NR unhelpful, only NMN did the job for her (Nicotinamide MonoNucleotide) .

That's really interesting. I see that nicotinamide needs roughly three enzymatic steps to get to NAD+, nicotinamide riboside needs two enzymatic steps to get to NAD+, and nicotinamide mononucleotide only needs one enzymatic step to get to NAD+.

I can certainly see how some people with different metabolisms might benefit from a vitamin that requires less processing...

Here what a doc is saying in 2010 about the Inositol Hexanicotinic Acid you are taking (the doc advises B3 for cardiovascular health in this article)

Thanks. Yeah, I'm now not a fan of Inositol Hexanicotinate. I will look at replacing it with nicotinamide for starters.

It's just so annoying because after searching for so long, this is the *only* B complex I found that had the right forms of the B vitamins, in reasonable quantities. Oh well!