Effects of chronic dietary nitrate supplementation on longevity, vascular function and cancer incidence in rats
Lucas Rannier R.A. Carvalho,
Drielle D. Guimarães,
Atalia Ferreira L. Flôr,
Ericka G. Leite,
Clara R. Ruiz,
Juliana T. de Andrade,
Matheus M.O. Monteiro,
Camille M. Balarini,
Ricardo Barbosa de Lucena,
Valeria Cristina Sandrim,
Jon O. Lundberg,
Eddie Weitzberg,
Mattias Carlström,
Valdir de Andrade Braga
Affiliations
Lucas Rannier R.A. Carvalho
Department of Physiology and Pharmacology - Karolinska Institutet, Stockholm, Sweden; Corresponding author. Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 5B, Solnavägen 10, 17177, Stockholm, Sweden.
Drielle D. Guimarães
Department of Physiology and Pharmacology - Karolinska Institutet, Stockholm, Sweden
Atalia Ferreira L. Flôr
Department of Biotechnology - Federal University of Paraiba, João Pessoa, Brazil
Ericka G. Leite
Department of Biotechnology - Federal University of Paraiba, João Pessoa, Brazil
Clara R. Ruiz
Department of Biotechnology - Federal University of Paraiba, João Pessoa, Brazil
Juliana T. de Andrade
Department of Biotechnology - Federal University of Paraiba, João Pessoa, Brazil
Matheus M.O. Monteiro
Department of Biotechnology - Federal University of Paraiba, João Pessoa, Brazil
Camille M. Balarini
Department of Biotechnology - Federal University of Paraiba, João Pessoa, Brazil
Ricardo Barbosa de Lucena
Department of Veterinary Science - Federal University of Paraiba, João Pessoa, Brazil
Valeria Cristina Sandrim
Department of Biophysics and Pharmacology - São Paulo State University, São Paulo, Brazil
Jon O. Lundberg
Department of Physiology and Pharmacology - Karolinska Institutet, Stockholm, Sweden
Eddie Weitzberg
Department of Physiology and Pharmacology - Karolinska Institutet, Stockholm, Sweden
Mattias Carlström
Department of Physiology and Pharmacology - Karolinska Institutet, Stockholm, Sweden
Valdir de Andrade Braga
Department of Biotechnology - Federal University of Paraiba, João Pessoa, Brazil; Corresponding author. Department of Biotechnology, Federal University of Paraiba, João Pessoa, Brazil.
Rationale: Dietary nitrate and nitrite have a notoriously bad reputation because of their proposed association with disease, in particular cancer. However, more recent lines of research have challenged this dogma suggesting that intake of these anions also possess beneficial effects after in vivo conversion to the vital signaling molecule nitric oxide. Such effects include improvement in cardiovascular, renal and metabolic function, which is partly mediated via reduction of oxidative stress. A recent study even indicates that low dose of dietary nitrite extends life span in fruit flies. Methods: In this study, 200 middle-aged Wistar rats of both sexes were supplemented with nitrate or placebo in the drinking water throughout their remaining life and we studied longevity, biochemical markers of disease, vascular reactivity along with careful determination of the cause of death. Results: Dietary nitrate did not affect life span or the age-dependent changes in markers of oxidative stress, kidney and liver function, or lipid profile. Ex vivo examination of vascular function, however, showed improvements in endothelial function in rats treated with nitrate. Neoplasms were not more common in the nitrate group. Conclusion: We conclude that chronic treatment with dietary nitrate does not affect life span in rats nor does it increase the incidence of cancer. In contrast, vascular function was improved by nitrate, possibly suggesting an increase in health span.