Increasing dietary nitrate has no effect on cancellous bone loss or fecal microbiome in ovariectomized rats

Abstract

ScopeStudies suggest diets rich in fruit and vegetables reduce bone loss, although the specific compounds responsible are unknown. Substrates for endogenous nitric oxide (NO) production, including organic nitrates and dietary nitrate, may support NO production in age‐related conditions, including osteoporosis. We investigated the capability of dietary nitrate to improve NO bioavailability, reduce bone turnover and loss.Methods and resultsSix‐month‐old Sprague Dawley rats [30 ovariectomized (OVX) and 10 sham‐operated (sham)] were randomized into three groups: (i) vehicle (water) control, (ii) low‐dose nitrate (LDN, 0.1 mmol nitrate/kg bw/day), or (iii) high‐dose nitrate (HDN, 1.0 mmol nitrate/kg bw/day) for three weeks. The sham received vehicle. Serum bone turnover markers; bone mass, mineral density, and quality; histomorphometric parameters; and fecal microbiome were examined. Three weeks of LDN or HDN improved NO bioavailability in a dose‐dependent manner. OVX resulted in cancellous bone loss, increased bone turnover, and fecal microbiome changes. OVX increased relative abundances of Firmicutes and decreased Bacteroideceae and Alcaligenaceae. Nitrate did not affect the skeleton or fecal microbiome.ConclusionThese data indicate that OVX affects the fecal microbiome and that the gut microbiome is associated with bone mass. Three weeks of nitrate supplementation does not slow bone loss or alter the fecal microbiome in OVX.

The Probiotic Lactobacillus fermentum Prevents Dysbiosis and Vascular Oxidative Stress in Rats with Hypertension Induced by Chronic Nitric Oxide Blockade

“…Prior works have demonstrated that dietary nitrate or exogenous NO exerts antimicrobial effects and can alter oral microbiome composition . However, dietary nitrates did not induced significant differences in fecal microbioma composition or diversity . In contrast to previous data showing no significant changes in gut microbiota after l ‐NAME treatment, we found that chronic inhibition of NO synthesis induced important changes in gut microbiota linked to hypertension.…”

Treatment with Nitrate, but Not Nitrite, Lowers the Oxygen Cost of Exercise and Decreases Glycolytic Intermediates While Increasing Fatty Acid Metabolites in Exercised Zebrafish

“…Whole blood collection was as previously published, except fluid volumes were modified to 2 µL blood and 18 µL ice-cold reverse-osmosis water for nitrate quantification or to 16 µL blood and a 4 µL stop solution for nitrite measurements. Nitrate and nitrite concentrations were determined by ozone chemiluminescence, as previously described, on a Sievers Nitric Oxide Analyzer (45, 46).…”

Supplementation with nitrate only modestly affects lipid and glucose metabolism in genetic and dietary-induced murine models of obesity

“…This suggestion is supported by the observation that NO production declines with age due to decreased eNosdependent NO synthesis. (37,38) In such a context, inorganic nitrate has been shown to alleviate the senescence-related decline in liver function. (39) Notably, group I, which did not receive supplemental nitrate in our study, still received nitrate, nitrite or NO (NOx) from consuming tap water (nitrate/nitrite content: <1.5 mg/L) and through dietary arginine (0.69%), the levels of which exceeded the recommendations for growing mice (<0.1% for mice, gaining 0.8 g/day, NRC).…”