Dietary nitrate reduces resting metabolic rate: a randomized, crossover study in humans.
BACKGROUND
Nitrate, which is an inorganic anion abundant in vegetables, increases the efficiency of isolated human mitochondria. Such an effect might be reflected in changes in the resting metabolic rate (RMR) and formation of reactive oxygen species. The bioactivation of nitrate involves its active accumulation in saliva followed by a sequential reduction to nitrite, nitric oxide, and other reactive nitrogen species.


OBJECTIVE
We studied effects of inorganic nitrate, in amounts that represented a diet rich in vegetables, on the RMR in healthy volunteers.


METHODS
In a randomized, double-blind, crossover study, we measured the RMR by using indirect calorimetry in 13 healthy volunteers after a 3-d dietary intervention with sodium nitrate (NaNO₃) or a placebo (NaCl). The nitrate dose (0.1 mmol · kg⁻¹ · d⁻¹) corresponded to the amount in 200-300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate. Effects of direct nitrite exposure on cell respiration were studied in cultured human primary myotubes.


RESULTS
The RMR was 4.2% lower after nitrate compared with placebo administration, and the change correlated strongly to the degree of nitrate accumulation in saliva (r² = 0.71). The thyroid hormone status, insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, and total antioxidant capacity were unaffected by nitrate. The administration of nitrite to human primary myotubes acutely inhibited respiration.


CONCLUSIONS
Dietary inorganic nitrate reduces the RMR. This effect may have implications for the regulation of metabolic function in health and disease.
Departments of Physiology and Pharmacology (FJL, TAS, MPM, JOL, and EW), Medical Biochemistry and Biophysics, Division of Physiological Chemistry II (AC and CEW), and Clinical Science and Education, Södersjukhuset (TN), Karolinska Institutet, Stockholm, Sweden, and the Åstrand Laboratory of Work Physiology, The Swedish School of Sport and Health Sciences, Stockholm, Sweden (BE).
Filip J
FJ
Larsen
Tomas A
TA
Schiffer
Björn
B
Ekblom
Mathias P
MP
Mattsson
Antonio
A
Checa
Craig E
CE
Wheelock
Thomas
T
Nyström
Jon O
JO
Lundberg
Eddie
E
Weitzberg
D000284:Administration, Oral; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D001481:Basal Metabolism; D015415:Biomarkers / Q000097:blood; D002153:Calorimetry, Indirect; D019069:Cell Respiration; D002478:Cells, Cultured; D018592:Cross-Over Studies; D004032:Diet / Q000009:adverse effects*; D004311:Double-Blind Method; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D009566:Nitrates / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000378:metabolism; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D018384:Oxidative Stress; D052097:Quadriceps Muscle / Q000166:cytology / Q000378:metabolism; D012463:Saliva / Q000378:metabolism
D015415:Biomarkers; D009566:Nitrates; D009573:Nitrites; C031618:sodium nitrate