Table 2.
High-intensity and long-duration studies.
| Investigators Year Published | Study Population | Analytical Platform/Matrix | Research Design | Key Findings Exercise Effect Separate from Other Interventions | Intensity |
|---|---|---|---|---|---|
| Nieman et al., 2015 [5] | 20 male cyclists (aged 39.2 ± 1.9 years) | UPLC-MS/MS; Plasma |
Randomized, cross-over design; three trials of a 75-km cycling protocol ingesting: water only, bananas and water, pears and water (2-week washout); blood samples timepoints: pre- and post-exercise (0-h, 1.5-h, 21-h) | 509 metabolites were chemically identified; ↑ ratio > 2-fold: 107 metabolites increased in the water only trial (exercise effects); ↑ ratio > 5-fold: 35 metabolites increased, all from the lipid super pathway, all significantly elevated 1.5-h post exercise, 8 only remained after 21-h post-exercise. | High-intensity, long-duration |
| Nieman et al., 2014* [7] | 19 male cyclists (aged 38.06 ± 1.6 years) | GC-MS and UHPLC-MS/MS; Plasma |
Randomized, cross-over design; two trials of a 75-km cycling protocol with pistachio or no pistachio supplementation (2-week washout); blood samples timepoints: pre- and post-exercise (0-h, 1.5-h, 21-h) | 423 metabolites were chemically identified; Exercise increased 167 metabolites; All but 26 of these metabolites were related to ↑ lipid and carnitine metabolism, with the largest fold changes seen for ketones, dicarboxylate fatty acids, and long chain fatty acids. | High-intensity, long-duration |
| Nieman et al., 2017 [8] | 24 trained male runners (aged 36.5 ± 1.8 years) | GC-MS and UHPLC-MS/MS; Plasma |
Repeated measures, ANOVA analysis, one group design; blood samples collected pre- and post-exercise (0-h), one bout run to exhaustion at 70%VO2max | 209 chemically identified metabolites changed with exercise, especially long and medium-chain ↑ fatty acids, ↑ fatty acids oxidation products (dicarboxylate and monohydroxy fatty acids and acylcarnitines), and ↑ ketone bodies. Minor relationship with ↑ IL-6. | High-intensity, long-duration |
| Davison et al., 2018 [9] | 24 healthy males (aged 28 ± 5 years) | LC-MS; Serum |
Double-blind, randomized, cross-over design; 60-min run 75% VO2max in hypoxia (FiO2 = 0.16%) (hypoxia chamber) and normoxia (FiO2 = 0.21%) (1-week washout); blood samples timepoints: pre- (after 30-min rest in hypoxia, normoxia), post-exercise (0 h, 3-h) | 27 metabolites, identified using internet databases, changed with exercise; Most related to ↑ lipid metabolism (several acylcarnitines molecules identified) and purine metabolism [↑adenine, ↑adenosine and ↓ (3 h after recovery) hypoxanthine]; ↑ 4.3-fold increase in 18 acylcarnitines post-exercise, above pre-exercise at 3-h recovery. | High-intensity, long-duration |
| Lehman et al., 2010 [12] | Healthy subjects; 1st study: n = 13 (32.6 ± 6.1 years) 2nd study: n = 8 (30.9 ± 5.8 years) | UPLC-qTOF-MS; Plasma |
Parallel group design; 1st study: treadmill run 60min at 75% VO2, blood samples timepoints: pre- and post-exercise (0-h, 3-h, 24-h); 2nd study: treadmill run > 120 min at 70%VIAT, blood samples timepoints: pre- (1h 45 min after breakfast) and post-exercise (0-h, 3-h, 24-h) | 10 metabolites, chemically identified, characterized the separation between the timepoints; Most part non-esterified free fatty acids; ↑ 9-fold increases in acylcarnitines. | High-intensity, long-duration |
| Lewis et al., 2010 [13] | 25 amateur runners (aged 42 ± 9 years) | LC-MS; Plasma |
Repeated measures, one group; Boston Marathon; blood samples time points: pre- and post-marathon | Metabolites chemically identified; ↑ in glycolysis, lipolysis, adenine nucleotide catabolism, and amino acid catabolism; ↑ indicators of glycogenolysis (glucose-6-phosphate and 3-phosphoglycerate), and small molecules that reflect oxidative stress (allantoin), and that modulate insulin sensitivity (niacinamide) | High-intensity, long-duration |
| Nieman et al., 2013 [14] | 35 long-distance male runners (supplemented group: aged 33.7 ± 6.8 years; placebo: aged 35.2 ± 8.7 years) | GC-MS and UHPLC-MS/MS; Serum |
Double-blind, parallel group design; 2-week supplementation (polyphenol-enriched protein) followed by a 3-day intensified exercise (2.5-h at 70%VO2max bouts); blood samples timepoints: pre- and post- 14-day supplementation, and immediately and 14-h after the 3rd day of running | 324 chemically identified metabolites that changed with 3-day period of exercise; ↑ metabolites related to fatty acid oxidation and ketogenesis including free fatty acids, acylcarnitines, 3-hydroxy-fatty acids, and dicarboxylic acids, amino acid and carbohydrate metabolism, energy production, nucleotides, and cofactors and vitamins. | High-intensity, long-duration |
| Knab et al., 2013 [16] | 9 elite male sprint and middle-distance swim athletes; 7 control subjects (healthy and exercised less than 150 min/week) (aged 24.6 ± 0.7 years) | GC-MS; Serum |
Randomized, crossover design, 10-day supplementation with juice (8 fl oz pre- and post-training) or non-juice, 10-d practice of 2-h swimming, approximately 5500-m swim interval training (3-week washout). Blood samples timepoints: pre- and post- each 10-days supplementation period and post-exercise (0-h) | 325 metabolites were chemically identified; No effects of juice on exercise-induced measures; ↑ Oxidative stress and ↓ antioxidant capacity in swimmers group compared to nonathletic control group; Metabolites that differed mostly related to substrate utilization and supplements used by the swimmers. Pre and post-exercise small but significant shift in metabolites related to substrate utilization: pyruvic acid, propanoic acid, d-fructose, mannose, n-acetylglutamine, norleucine, alloisoleucine, and d-glucuronic acid. | High-intensity, long-duration |
| Manaf et al., 2018 [17] | 18 healthy and recreationally active males (aged 24.7 ± 4.8 years) | LC-MS; Plasma |
Repeated measures, ANOVA analysis, one group design; time-to-exhaustion (81-min) cycling test at a workload 3 mM/l lactate; blood samples timepoints: pre-exercise, during exercise (10-min, before fatigue), point of exhaustion (immediately after fatigue), post-exercise (20-min after fatigue) | 80 metabolites identified using internet databases; 68 metabolites changed during exercise; ↑ Free-fatty acids and ↓ tryptophan contributed to differences in plasma metabolome at fatigue. | High-intensity, long-duration |
| Messier et al., 2017 [18] | 20 healthy male (aged 39 ± 4.3 years) | 1H NMR; Plasma |
Cross-over design; cycling 60-min at ventilatory threshold 1 at 70 rpm, at sea level and above 2150 m of the sea level (2-week washout); blood samples timepoints: pre- and post-exercise (0-h) | 18 metabolites identified using internet databases; ↓ glucose and free amino acid levels; No differences in lipid metabolism between altitudes; Fuel shift from lipid oxidation to carbohydrate oxidation at 2150 above sea level. | High-intensity, long-duration |
| Nieman et al., 2013 [19] | 15 runners (7 males, 8 females) (aged 35.2 ± 8.7 years) | GC-MS and UHPLC-MS/MS; Serum |
Cross-sectional design, 3-day period exercise (2.5 h per day running bouts at approximately 70% VO2max); blood samples timepoints: pre- and post-exercise (0-h, 14-h) | Metabolites chemically identified; ↑ ≥ 2-fold increases in 75 metabolites immediately post 3-day exercise period, 22 related to lipid/carnitine metabolism, 13 related to amino acid/peptide metabolism, 4 to hemoglobin/porphyrin metabolism, and 3 to Krebs cycle intermediates. After 14-h recovery: 50 of 75 metabolites still elevated. ↓ 22 metabolites post-exercise related to lysolipid and bile acid metabolism. | High-intensity, long-duration |
| Nieman et al., 2014* [20] | 19 male cyclists (aged 38.06 ± 1.6 years) | GC-MS and UHPLC-MS/MS; Plasma |
Repeated measures, ANOVA analysis, one group design; blood samples timepoints: pre- and post-exercise (0-h, 1.5-h, 21-h); 75-km cycling protocol | 221 chemically identified metabolites changed with exercise; all but 26 related to ↑ lipid and carnitine metabolism; largest fold changes seen for ↑ ketones, dicarboxylate fatty acids, and long chain fatty acids. | High-intensity, long-duration |
| Ra et al., 2014 [21] | 37 male soccer players (aged 20.6 ± 0.04 years) | CE-TOFMS; Saliva |
Repeated measures, ANOVA analysis, one group design; 3-day game program (90-min per day); saliva samples timepoints: pre-exercise (1-month before) and post-exercise (24-h after) | 144 metabolites chemically identified; ↑12 metabolites (e.g., 3-methylhistidine, glucose 1- and 6-phosphate, taurine, amino acids) related to muscle catabolism, glucose metabolism, lipid metabolism, amino acid metabolism and energy metabolism. | High-intensity, long-duration |
| Stander et al., 2018 [22] | 31 recreational marathon athletes (19 males and 12 females) (aged 41 ± 12 years) | GC-TOFMS; Serum |
Repeated measures, ANOVA analysis, one group design; 42-km marathon; blood samples timepoints: pre- and post-marathon (0-h) | 70 metabolites chemically identified; ↑ carbohydrates, fatty acids, tricarboxylic acid cycle intermediates, ketones, and ↓ amino acids; ↑odd-chain fatty acids and α-hydroxy acids. | High-intensity, long-duration |
| Howe et al., 2018 [24] | 9 male ultramarathon runners (aged 34 ± 7 years) | HILIC-MS; Plasma |
Repeated measures, ANOVA analysis, one group design; 80.5-km treadmill simulated ultramarathon run; blood samples timepoints: pre- and post-exercise (0-h) | 446 metabolites chemically identified; ↓ amino acids metabolism post-80.5 km; ↑ in the formation of medium-chain unsaturated, partially oxidized fatty acids and conjugates of fatty acids with carnitines. | High-intensity, long-duration |
UPLC-MS: ultra-performance liquid chromatography mass spectrometry; UHPLC-MS: ultra-high-performance liquid chromatography mass spectrometry; GC-MS: gas chromatography mass spectrometry; LC-MS: liquid chromatography mass spectrometry; UHPLC/Q-TOF MS: ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry; 1H NMR: proton nuclear magnetic resonance; CE-TOFMS: capillary electrophoresis time-of-flight mass spectrometry; HILIC-MS: hydrophilic interaction chromatography mass spectrometry; VO2max = maximal oxygen uptake; FiO2 = fraction of inspired oxygen; VIAT = velocity at individual anaerobic threshold. * References [7,20] were from the same study but the data sets provided additive information.