PMID- 36364742
OWN - NLM
STAT- MEDLINE
DCOM- 20221114
LR  - 20230308
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 14
IP  - 21
DP  - 2022 Oct 25
TI  - Effects of Combined Inorganic Nitrate and Nitrite Supplementation on 
      Cardiorespiratory Fitness and Skeletal Muscle Oxidative Capacity in Type 2 
      Diabetes: A Pilot Randomized Controlled Trial.
LID - 10.3390/nu14214479 [doi]
LID - 4479
AB  - Nitric oxide (NO) stimulates mitochondrial biogenesis in skeletal muscle. 
      However, NO metabolism is disrupted in individuals with type 2 diabetes mellitus 
      (T2DM) potentially contributing to their decreased cardiorespiratory fitness 
      (i.e., VO2max) and skeletal muscle oxidative capacity. We used a randomized, 
      double-blind, placebo-controlled, 8-week trial with beetroot juice containing 
      nitrate (NO3-) and nitrite (NO2-) (250 mg and 20 mg/day) to test potential 
      benefits on VO2max and skeletal muscle oxidative capacity in T2DM. T2DM (N = 36, 
      Age = 59 +/- 9 years; BMI = 31.9 +/- 5.0 kg/m2) and age- and BMI-matched non-diabetic 
      controls (N = 15, Age = 60 +/- 9 years; BMI = 29.5 +/- 4.6 kg/m2) were studied. 
      Mitochondrial respiratory capacity was assessed in muscle biopsies from a 
      subgroup of T2DM and controls (N = 19 and N = 10, respectively). At baseline, 
      T2DM had higher plasma NO3- (100%; p < 0.001) and lower plasma NO2- levels 
      (-46.8%; p < 0.0001) than controls. VO2max was lower in T2DM (-26.4%; p < 0.001), 
      as was maximal carbohydrate- and fatty acid-supported oxygen consumption in 
      permeabilized muscle fibers (-26.1% and -25.5%, respectively; p < 0.05). 
      NO3-/NO2- supplementation increased VO2max (5.3%; p < 0.01). Further, circulating 
      NO2-, but not NO3-, positively correlated with VO2max after supplementation (R2= 
      0.40; p < 0.05). Within the NO3-/NO2- group, 42% of subjects presented 
      improvements in both carbohydrate- and fatty acid-supported oxygen consumption in 
      skeletal muscle (vs. 0% in placebo; p < 0.05). VO2max improvements in these 
      individuals tended to be larger than in the rest of the NO3-/NO2- group (1.21 +/- 
      0.51 mL/(kg*min) vs. 0.31 +/- 0.10 mL/(kg*min); p = 0.09). NO3-/NO2- 
      supplementation increases VO2max in T2DM individuals and improvements in skeletal 
      muscle oxidative capacity appear to occur in those with more pronounced increases 
      in VO2max.
FAU - Turner, Kristen D
AU  - Turner KD
AUID- ORCID: 0000-0003-4418-5281
AD  - Department of Health and Human Physiology, College of Liberal Arts and Sciences, 
      University of Iowa, Iowa City, IA 52242, USA.
FAU - Kronemberger, Ana
AU  - Kronemberger A
AD  - Department of Health and Human Physiology, College of Liberal Arts and Sciences, 
      University of Iowa, Iowa City, IA 52242, USA.
FAU - Bae, Dam
AU  - Bae D
AD  - Department of Health and Human Physiology, College of Liberal Arts and Sciences, 
      University of Iowa, Iowa City, IA 52242, USA.
FAU - Bock, Joshua M
AU  - Bock JM
AD  - Department of Physical Therapy and Rehabilitation Science, Carver College of 
      Medicine, University of Iowa, Iowa City, IA 52242, USA.
FAU - Hughes, William E
AU  - Hughes WE
AD  - Department of Physical Therapy and Rehabilitation Science, Carver College of 
      Medicine, University of Iowa, Iowa City, IA 52242, USA.
FAU - Ueda, Kenichi
AU  - Ueda K
AUID- ORCID: 0000-0002-4559-4581
AD  - Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa 
      City, IA 52242, USA.
FAU - Feider, Andrew J
AU  - Feider AJ
AD  - Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa 
      City, IA 52242, USA.
FAU - Hanada, Satoshi
AU  - Hanada S
AUID- ORCID: 0000-0002-6205-3146
AD  - Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa 
      City, IA 52242, USA.
FAU - de Sousa, Luis G O
AU  - de Sousa LGO
AUID- ORCID: 0000-0003-1013-2595
AD  - Department of Internal Medicine, Carver College of Medicine, University of Iowa, 
      Iowa City, IA 52242, USA.
FAU - Harris, Matthew P
AU  - Harris MP
AUID- ORCID: 0000-0002-8078-3847
AD  - Department of Health and Human Physiology, College of Liberal Arts and Sciences, 
      University of Iowa, Iowa City, IA 52242, USA.
FAU - Anderson, Ethan J
AU  - Anderson EJ
AUID- ORCID: 0000-0002-0113-8875
AD  - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of 
      Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
AD  - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa 
      City, IA 52242, USA.
AD  - Francois M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, 
      IA 52242, USA.
FAU - Bodine, Sue C
AU  - Bodine SC
AD  - Department of Internal Medicine, Carver College of Medicine, University of Iowa, 
      Iowa City, IA 52242, USA.
AD  - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa 
      City, IA 52242, USA.
FAU - Zimmerman, M Bridget
AU  - Zimmerman MB
AD  - Department of Biostatistics, College of Public Health, University of Iowa, Iowa 
      City, IA 52242, USA.
FAU - Casey, Darren P
AU  - Casey DP
AD  - Department of Physical Therapy and Rehabilitation Science, Carver College of 
      Medicine, University of Iowa, Iowa City, IA 52242, USA.
AD  - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa 
      City, IA 52242, USA.
AD  - Francois M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, 
      IA 52242, USA.
AD  - Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 
      52242, USA.
FAU - Lira, Vitor A
AU  - Lira VA
AUID- ORCID: 0000-0002-3162-3804
AD  - Department of Health and Human Physiology, College of Liberal Arts and Sciences, 
      University of Iowa, Iowa City, IA 52242, USA.
AD  - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa 
      City, IA 52242, USA.
AD  - Francois M. Abboud Cardiovascular Research Center, University of Iowa, Iowa City, 
      IA 52242, USA.
AD  - Obesity Research and Education Initiative, University of Iowa, Iowa City, IA 
      52242, USA.
LA  - eng
GR  - R56 AG063820/AG/NIA NIH HHS/United States
GR  - 1-16-1CTS-015/American Diabetes Association/
GR  - CA086862/NH/NIH HHS/United States
GR  - AG063820/NH/NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20221025
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Nitrites)
RN  - 0 (Nitrates)
RN  - S7G510RUBH (Nitrogen Dioxide)
RN  - 0 (Nitrogen Oxides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 0 (Fatty Acids)
RN  - 0 (Carbohydrates)
SB  - IM
MH  - Humans
MH  - Middle Aged
MH  - Aged
MH  - Nitrites
MH  - Nitrates
MH  - *Cardiorespiratory Fitness
MH  - *Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Nitrogen Dioxide/metabolism/pharmacology
MH  - Pilot Projects
MH  - Muscle, Skeletal/metabolism
MH  - Nitrogen Oxides/metabolism
MH  - Nitric Oxide/metabolism
MH  - Double-Blind Method
MH  - Dietary Supplements
MH  - Fatty Acids/metabolism
MH  - Carbohydrates/pharmacology
MH  - Oxidative Stress
MH  - *Beta vulgaris
PMC - PMC9654804
OTO - NOTNLM
OT  - mitochondria
OT  - nutraceutical
OT  - oxygen consumption
COIS- The authors declare no conflict of interest.
EDAT- 2022/11/12 06:00
MHDA- 2022/11/15 06:00
PMCR- 2022/10/25
CRDT- 2022/11/11 01:44
PHST- 2022/10/01 00:00 [received]
PHST- 2022/10/16 00:00 [revised]
PHST- 2022/10/20 00:00 [accepted]
PHST- 2022/11/11 01:44 [entrez]
PHST- 2022/11/12 06:00 [pubmed]
PHST- 2022/11/15 06:00 [medline]
PHST- 2022/10/25 00:00 [pmc-release]
AID - nu14214479 [pii]
AID - nutrients-14-04479 [pii]
AID - 10.3390/nu14214479 [doi]
PST - epublish
SO  - Nutrients. 2022 Oct 25;14(21):4479. doi: 10.3390/nu14214479.