Proof-of-principle That NAD+ Deficiency Exists In Humans

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"Our results are a proof-of-principle that NAD+ deficiency exists in humans and that NAD+ boosters can delay progression of mitochondrial muscle disease," Suomalainen-Wartiovaara comments.

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

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


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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.


Vitamin B3 revitalizes energy metabolism in muscle disease

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

zarrin77

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Btw, proanthocyanidins and other polyphenols can drastically increase NAD+ and the NAD/NADH ratio:
Dietary proanthocyanidins boost hepatic NAD+ metabolism and SIRT1 expression and activity in a dose-dependent manner in healthy rats

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Would likely work well with a precursor such as niacin.

Similarly, proanthocyanidins have been shown to increase the benefits of exercise (unlike traditional antioxidants like vitamin C and E, which can *negate* the benefits of exercise:
Combination of nutritional polyphenols supplementation with exercise training counteracts insulin resistance and improves endurance in high-fat diet-induced obese rats
 
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So French grape seed extract OPC or nicotinamide riboside would be useful?

Since OPC is both a fat-soluble and water-soluble antioxidant, it can neutralize a range of free radicals like no other agent. Furthermore, OPC acts 40 to 50 times more potently than Vitamin E, 10 times more so than Vitamin A and 18 times more so than Vitamin C

OPC is completely absorbed into the blood through the mucous membranes of the mouth and the stomach within minutes. This substance then reaches every organ, every component of tissue. Even skin, hair and nails. OPC reaches the highest concentration in the blood in just 45 minutes, and works for 72 hours

The higher the ORAC value the better.
 
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LeeLemonoil

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The caveat is that the rise in energy goes for senescent cells too.

B3 is also a good immune-booster
 

Pulstar

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In the context of the study, mentioned in the first post, is there a difference between niacin and niacinamide?
 

zarrin77

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In the context of the study, mentioned in the first post, is there a difference between niacin and niacinamide?

Yes, they only used niacin. The findings *might* translate to niacinamide as well. Some rodent studies show that they do, but afaik, this is the first human study we’ve got (besides nicotinamide riboside).

Niacin has some other independent benefits. It is profoundly anti-inflammatory and pro-resolving of inflammation by activating GPR109a receptor (the same receptor for butyrate and beta-hydroxybutyrate). This receptor has been shown to play a major role in metabolism. Niacinamide does NOT activiate this receptor.

Niacin fine-tunes energy homeostasis through canonical GPR109A signaling
https://www.fasebj.org/doi/full/10.1096/fj.201801951R
 

Vinny

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So French grape seed extract OPC or nicotinamide riboside would be useful?

Since OPC is both a fat-soluble and water-soluble antioxidant, it can neutralize a range of free radicals like no other agent. Furthermore, OPC acts 40 to 50 times more potently than Vitamin E, 10 times more so than Vitamin A and 18 times more so than Vitamin C

OPC is completely absorbed into the blood through the mucous membranes of the mouth and the stomach within minutes. This substance then reaches every organ, every component of tissue. Even skin, hair and nails. OPC reaches the highest concentration in the blood in just 45 minutes, and works for 72 hours

The higher the ORAC value the better.
What is OPC?
 

Tarmander

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Cool study. I have been using Niacin recently and it definitely helps with working out
 

Vinny

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Vinny

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Cool study. I have been using Niacin recently and it definitely helps with working out
How much do you take daily, Tarmander?
Thanks
 

LeeLemonoil

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Essential reading on that topic to set NAD+ increase in context. It isn’t universally healthy if you’re old or seriously ill
Beta-Lapachone is a key component in keeping the NAD+-benefits in such contexts via NQ01-gene


 

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