Resistance Exercise Reduces Kynurenine Pathway Metabolites in Breast Cancer Patients Undergoing Radiotherapy

Zimmer, Philipp; Schmidt, Martina E.; Prentzell, Mirja Tamara; Berdel, Bianca; Wiskemann, Joachim; Kellner, Karl Heinz; Debus, Jürgen; Ulrich, Cornelia M.; Opitz, Christiane A.; Steindorf, Karen

doi:10.3389/fonc.2019.00962

Cited by 38 publications

(41 citation statements)

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“…To our knowledge, this is the first study that explored the effects of resistance exercise training in the context of kynurenine metabolism pathway in pancreatic cancer patients. The findings are in accordance with our previous study on breast cancer patients showing that chronic resistance exercise counteracts increase in KYN levels and KTR (IDO/TDO) activity during adjuvant radiotherapy [22]. The results reveal that Supervised resistance exercise training can reduce serum KTR (indication of enzyme IDO/TDO) levels compared to Home-based group over time.…”

Section: Discussionsupporting

confidence: 92%

“…In conclusion, our results suggest that Supervised resistance exercise can downregulate the KTR (IDO/TDO) levels and, hence, may reduce possible disease progression in pancreatic cancer patients undergoing chemotherapy, confirming our earlier findings [22]. Further research in this direction is necessary to clarify the clinical relevance of whether physical exercise can mimic immune therapy and can finally inhibit IDO/TDO.…”

Section: Discussionsupporting

confidence: 89%

“…As already mentioned above, all these cell lines are influenced by KYN or its metabolites. We have recently shown that resistance exercise during radiotherapy can counteract radiation associated increase in KYN levels and IDO/TDO activity in breast cancer patients [22].…”

Section: Introductionmentioning

confidence: 99%

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Resistance Exercise Modulates Kynurenine Pathway in Pancreatic Cancer Patients

et al. 2020

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The aim of this study was to investigate the impact of Supervised and Home-based resistance exercise on the Kynurenine pathway in patients with pancreatic cancer who underwent surgery and chemotherapy. In the SUPPORT study, adult pancreatic cancer patients were randomized to intervention programs of 6-month (1) a Supervised moderate-to-high-intensity progressive resistance training or (2) unsupervised Home-based resistance training, or (3) to a standard care patient Control group. Serum levels of kynurenine, tryptophan and IL-6 were assessed for 32 participants before, after 3 months and after 6 months of exercise intervention. Group differences were investigated using analysis-of-covariance. Patients in the Supervised training group showed decreased levels of serum kynurenine and kynurenine/tryptophan ratio (p = 0.07; p = 0.01 respectively) as well as increased Tryptophan levels (p = 0.05) in comparison to Home-based and Control group over time. The Home-based exercise group had significant increased kynurenine and kynurenine/tryptophan ratio levels. IL-6 levels decreased over the first three months for both intervention groups as well as the Control group (Supervised: p < 0.01, Home-based: p < 0.010, Control group: p < 0.01). Supervised resistance exercise might positively regulate the Kynurenine pathway and downregulate the kynurenine/tryptophan (indicative of IDO/TDO enzyme) levels, hence modulating the immune system.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

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Resistance Exercise Modulates Kynurenine Pathway in Pancreatic Cancer Patients

et al. 2020

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“…However, as discussed by Fernestrom et al [59], even under conditions of supplementation with extra-Trp, no effect attributable to quinolinic acid toxicity have never been observed in humans. In addition, physical exercise has been shown to prevent per se the eventual brain entry of Trp-derived kynurenine [60] as well as to attenuate the activity of the kynurenine pathway [61,62].…”

Section: Discussionmentioning

confidence: 99%

Effects of a commercially available branched-chain amino acid-alanine-carbohydrate-based sports supplement on perceived exertion and performance in high intensity endurance cycling tests

Gervasi

Sisti

Amatori

et al. 2020

Journal of the International Society of Sports Nutrition

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Background: Sports nutritional supplements containing branched-chain amino acids (BCAA) have been widely reported to improve psychological and biological aspects connected to central fatigue and performance in endurance exercise, although the topic is still open to debate. The aim of the present study was to determine whether the intake of a commercially available BCAA-based supplement, taken according to the manufacturer's recommendations, could affect the rating of perceived exertion (RPE) and performance indexes at the beginning (1d) and end of a 9-week (9w) scheduled high intensity interval training program, with an experimental approach integrating the determination of psychometric, performance, metabolic and blood biochemical parameters. Methods: This was a randomized double-blind placebo-controlled study. Thirty-two untrained, healthy young adults (20 males and 12 female) were enrolled. A high-intensity endurance cycling (HIEC) test was used to induce fatigue in the participants: HIEC consisted in ten 90 s sprints interspersed by ten 3 min recovery phases and followed by a final step time to exhaustion was used. In parallel with RPE, haematological values (creatine kinase, alanine, BCAA, tryptophan, ammonia and glucose levels), and performance indexes (maximal oxygen consumption-VO 2max , power associated with lactate thresholds-W LT1 , W LT2 and time to exhaustion-TTE) were assessed. All subject took the supplement (13.2 g of carbohydrates; 3.2 g of BCAA and 1.6 g of L-alanine per dose) or placebo before each test and training session. Dietary habits and training load were monitored during the entire training period. Results: The administration of the supplement (SU) at 1d reduced RPE by 9% during the recovery phase, as compared to the placebo (PL); at 9w the RPE scores were reduced by 13 and 21% during the sprint and recovery phase, respectively; at 9w, prolonged supplement intake also improved TTE and TRIMP. SU intake invariably promoted a rapid increase (within 1 h) of BCAA serum blood levels and prevented the post-HIEC tryptophan: BCAA ratio increase found in the PL group, at both 1d and 9w. There was no difference in dietary habits between groups and those habits did not change over time; no difference in glycemia was found between SU and PL. VO 2max , W LT1 and W LT2 values improved over time, but were unaffected by supplement intake.

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“…Indeed, Agudelo and colleagues (2014) revealed that the increase in KATs led to a peripheral KYN clearance and thereby mediated resilience to stress-induced depression. However, to the best of our knowledge, only one study in humans showed a counteracting effect of regular exercise on peripheral KYN accumulation investigating resistance exercise in breast cancer patients undergoing radiotherapy (Zimmer et al 2019). Several other studies on regular (mainly aerobic) exercise in different populations did not observe alterations in circulating KYN pathway metabolites (Hennings et al 2013;Kuster et al 2017;Millischer et al 2017).…”

Section: Introductionmentioning

confidence: 71%

Acute hypertrophic but not maximal strength loading transiently enhances the kynurenine pathway towards kynurenic acid

et al. 2020

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Purpose Due to distinct immuno-and neuro-modulatory properties, growing research interest focuses on exercise-induced alterations of the kynurenine (KYN) pathway in healthy and clinical populations. To date, knowledge about the impact of different acute strength exercise modalities on the KYN pathway is scarce. Therefore, we investigated the acute effects of hypertrophic (HYP) compared to maximal (MAX) strength loadings on the KYN pathway regulation. Methods Blood samples of twelve healthy males (mean age and weight: 23.5 ± 3.2 years; 77.5 ± 7.5 kg) were collected before (T 0), immediately after (T 1), and 1 h after completion (T 2) of HYP (5 sets with 10 repetitions at 80% of 1RM) and MAX (15 sets with 1RM) loadings performed in a randomized cross-over design. Serum concentrations of tryptophan (TRP), KYN, kynurenic acid (KA), and quinolinic acid (QA) were assessed using high-performance liquid chromatography. Results The KA/KYN ratio increased from T 0 to T 1 (p = 0.01) and decreased from T 1 to T 2 (p = 0.011) in HYP, while it was maintained within MAX. Compared to MAX, serum concentrations of KA were greater in HYP at T 1 (p = 0.014). Moreover, the QA/KA ratio was significantly lower in HYP than in MAX at T 1 (p = 0.002). Conclusion Acute HYP loading led to increases in the metabolic flux yielding KA, thereby possibly promoting immunosuppression and neuroprotection. Our findings emphasize the potential of acute HYP exercise as short-term modulator of KYN pathway downstream to KA in healthy males and need to be proven in other samples.

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Resistance Exercise Reduces Kynurenine Pathway Metabolites in Breast Cancer Patients Undergoing Radiotherapy

Cited by 38 publications

References 55 publications

Resistance Exercise Modulates Kynurenine Pathway in Pancreatic Cancer Patients

Resistance Exercise Modulates Kynurenine Pathway in Pancreatic Cancer Patients

Effects of a commercially available branched-chain amino acid-alanine-carbohydrate-based sports supplement on perceived exertion and performance in high intensity endurance cycling tests

Acute hypertrophic but not maximal strength loading transiently enhances the kynurenine pathway towards kynurenic acid

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