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

Authors :
Pirinen E
Auranen M
Khan NA
Brilhante V
Urho N
Pessia A
Hakkarainen A
Kuula J
Heinonen U
Schmidt MS
Haimilahti K
Piirilä P
Lundbom N
Taskinen MR
Brenner C
Velagapudi V
Pietiläinen KH
Suomalainen A
Source :
Cell metabolism [Cell Metab] 2020 Jun 02; Vol. 31 (6), pp. 1078-1090.e5. Date of Electronic Publication: 2020 May 07.
Publication Year :
2020

Abstract

NAD <superscript>+</superscript> is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD <superscript>+</superscript> depletion occurs in patients with degenerative disorders and whether NAD <superscript>+</superscript> repletion improves their symptoms has remained open. Here, we report systemic NAD <superscript>+</superscript> deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD <superscript>+</superscript> -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 <superscript>+</superscript> increased in all subjects, up to 8-fold, and muscle NAD <superscript>+</superscript> 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 <superscript>+</superscript> deficiency and points niacin to be an efficient NAD <superscript>+</superscript> booster for treating mitochondrial myopathy.<br />Competing Interests: Declaration of Interests A.S. has filed a patent application for a method that allows NAD(+) analysis from the blood and tissue samples. C.B. is the inventor of intellectual property on the nutritional and therapeutic uses of NR. He serves as chief scientific advisor of ChromaDex, which licensed, developed, and commercialized NR technologies and holds stock in ChromaDex. The other authors declare no competing interests.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1932-7420
Volume :
31
Issue :
6
Database :
MEDLINE
Journal :
Cell metabolism
Publication Type :
Academic Journal
Accession number :
32386566
Full Text :
https://doi.org/10.1016/j.cmet.2020.04.008