{"doi":"10.3390/nu14214479","title":"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","abstract":"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.","journal":"Nutrients","year":2022,"id":262529,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":893732,"name":"Ana Kronemberger","orcid":"0000-0002-7147-6992","position":1,"is_corresponding":false},{"id":918927,"name":"Dam Bae","orcid":null,"position":2,"is_corresponding":false},{"id":641711,"name":"Joshua M. Bock","orcid":"0000-0002-0101-0900","position":3,"is_corresponding":false},{"id":918310,"name":"William E. Hughes","orcid":"0000-0003-2064-4834","position":4,"is_corresponding":false},{"id":778272,"name":"Kenichi Ueda","orcid":"0000-0002-4559-4581","position":5,"is_corresponding":false},{"id":778273,"name":"Andrew J. Feider","orcid":"0000-0002-7620-6537","position":6,"is_corresponding":false},{"id":778274,"name":"Satoshi Hanada","orcid":"0000-0002-6205-3146","position":7,"is_corresponding":false},{"id":918311,"name":"Luís Gustavo Oliveira de Sousa","orcid":"0000-0003-1013-2595","position":8,"is_corresponding":false},{"id":739852,"name":"Matthew P. Harris","orcid":"0000-0002-8078-3847","position":9,"is_corresponding":false},{"id":605473,"name":"Ethan J. Anderson","orcid":"0000-0002-0113-8875","position":10,"is_corresponding":false},{"id":317187,"name":"Sue C. Bodine","orcid":"0000-0002-5742-9145","position":11,"is_corresponding":false},{"id":701258,"name":"M. Bridget Zimmerman","orcid":null,"position":12,"is_corresponding":false},{"id":778275,"name":"Darren P. Casey","orcid":"0000-0003-4564-8604","position":13,"is_corresponding":false},{"id":612656,"name":"Vitor A. Lira","orcid":"0000-0002-3162-3804","position":14,"is_corresponding":false},{"id":918309,"name":"Kristen Turner","orcid":"0000-0003-4418-5281","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:26:25.074177Z","pmid":"36364742","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}