Taking protein or amino acids postexercise might reduce inflammation and oxidative stress Original paper

This systematic review found that supplementation with protein or amino acids reduced postexercise inflammation or oxidative stress in some (but not most) studies. This inconsistency may be due to study heterogeneity, insufficient sensitivity (biomarker assessment), or insufficient power (study controls and analysis).

This Study Summary was published on May 3, 2022.

Background

Inflammation and reactive oxygen species (ROS) are necessary and important modes of signaling for muscle adaptation and regeneration, but they can also cause damage if left unchecked. Proper protein intake is crucial for recovery from exercise, and some animal studies suggest that protein has antioxidant and anti-inflammatory effects. Can it affect postexercise inflammation and oxidative stress in humans?

The study

This systematic review of 34 randomized controlled trials involved healthy adult participants (99% male, average age of 24) who underwent postexercise interventions consisting of whole protein (18 studies on whey, milk, etc.) or supplemental amino acid (16 studies on mixed amino acids, glutamine, taurine, etc.). The control interventions were flavored water, a carbohydrate beverage, or a sugar pill.

Study sample sizes ranged from 8 to 40 participants. Nineteen of the studies recruited trained athletes, 9 recruited recreationally active participants, and 6 recruited untrained participants.

Postexercise (less than 96 hours) markers of inflammation and oxidative stress included tissue sample levels of cytokines (e.g., interleukin-6, tumor necrosis factor-alpha), C-reactive protein, 8-hydroxydeoxyguanosine (an indicator of DNA damage), and total antioxidant capacity, among others.

The results

Most studies (20) did not demonstrate changes in postexercise levels of inflammatory or oxidative stress markers when compared to controls. Five studies on whole protein and 9 studies on supplemental amino acid interventions reported either anti-inflammatory or antioxidant effects in some markers when compared to controls.

Note

These results should be interpreted with caution for the following reasons:

  • The study designs were very inconsistent, with varying doses, durations, whole protein or amino acid sources, and population characteristics.
  • The intervention and diet were not always properly controlled, which could indirectly influence biomarkers of inflammation and oxidative stress.[8]
  • Only a few biomarkers were measured in each study, and many can be very sensitive or dependent on the specific assay or sample used.[9][10]
  • Several studies did not include these measurements as primary outcomes and were likely not sufficiently powered to detect differences.

The big picture

Protein’s purported antioxidant effects are partially explained by its ability to enhance the availability of glutathione, a cofactor involved in the endogenous antioxidant response. It has also been shown to dampen inflammatory signaling, but the reports fueling these purported effects are primarily from animal and cell studies.[11][12] One human study that reported an antioxidant benefit involved a special carbohydrate and whey protein cake. In this case, not only does the combination with carbohydrate make it difficult to determine whether benefits were derived from the protein, carbohydrate, or both, but the participants also underwent “exhaustive cycling.”[13] There may be more nuance to this relationship, such as the existence of an effect only following excess high-intensity exercise (or overtraining) that may trigger a high level of oxidative stress and oxidative distress.

There is also some controversy regarding whether antioxidant supplementation may interfere with redox signaling and blunt exercise-induced adaptation and recovery. A well-designed 11-week RCT from 2014 reported that supplementation with the antioxidants vitamins C and E decreased markers of exercise-induced cellular adaptation despite no difference in performance measures when compared to placebo.[14] A meta-analysis from 2020 reported that vitamin C and/or E supplementation that lasted more than 4 weeks did not influence aerobic or resistance training-induced adaptations in physiological function.[15] A systematic review from 2022 reported that antioxidant supplementation before or during exercise can delay fatigue, reduce muscle damage, and decrease recovery time, [16] while a Cochrane systematic review from 2020 reported that antioxidant supplementation does not result in a clinically relevant reductions of muscle soreness.[17]

While novel, more precise tools are being developed to allow for a greater understanding of redox signaling and intricate cell communication, it appears that more research is needed to understand the subtlety in the relationship between exercise-induced ROS, adaptation, and protein supplementation. Since most of the underlying mechanisms involved in these relationships have been explored in animal models (some have yet to be proven) and studies are limited by various aspects of intervention (e.g., exercise duration, type, intensity), sample type (i.e., systemic vs. localized), measurement methods, and sensitivity (e.g., differences in hydration are not always monitored but can influence concentrations of analytes), the specifics are still being teased out.[2] [6][10] Alternatively, the null result may very well suggest that exercise-induced oxidative stress and inflammation are an important stimulus for muscle adaptation.

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This Study Summary was published on May 3, 2022.

References

  1. ^Panday A, Sahoo MK, Osorio D, Batra SNADPH oxidases: an overview from structure to innate immunity-associated pathologiesCell Mol Immunol.(2015 Jan)
  2. ^Jessica Bouviere, Rodrigo S Fortunato, Corinne Dupuy, Joao Pedro Werneck-de-Castro, Denise P Carvalho, Ruy A LouzadaExercise-Stimulated ROS Sensitive Signaling Pathways in Skeletal MuscleAntioxidants (Basel).(2021 Mar 30)
  3. ^Cobley JN, Close GL, Bailey DM, Davison GWExercise redox biochemistry: Conceptual, methodological and technical recommendationsRedox Biol.(2017 Aug)
  4. ^Helmut SiesOxidative eustress: On constant alert for redox homeostasisRedox Biol.(2021 May)
  5. ^Minna Tanskanen, Mustafa Atalay, Arja UusitaloAltered oxidative stress in overtrained athletesJ Sports Sci.(2010 Feb)
  6. ^Érica Cerqueira, Daniel A Marinho, Henrique P Neiva, Olga LourençoInflammatory Effects of High and Moderate Intensity Exercise-A Systematic ReviewFront Physiol.(2020 Jan 9)
  7. ^Anand Thirupathi, Yaodong Gu, Ricardo Aurino PinhoExercise Cuts Both Ways with ROS in Remodifying Innate and Adaptive Responses: Rewiring the Redox Mechanism of the Immune System during ExerciseAntioxidants (Basel).(2021 Nov 21)
  8. ^Krasimira Aleksandrova, Liselot Koelman, Caue Egea RodriguesDietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studiesRedox Biol.(2021 Jun)
  9. ^Ilaria Marrocco, Fabio Altieri, Ilaria PelusoMeasurement and Clinical Significance of Biomarkers of Oxidative Stress in HumansOxid Med Cell Longev.(2017)
  10. ^Karen M O'Callaghan, Daniel E RothStandardization of laboratory practices and reporting of biomarker data in clinical nutrition researchAm J Clin Nutr.(2020 Aug 1)
  11. ^R Xu, N Liu, X Xu, B KongAntioxidative effects of whey protein on peroxide-induced cytotoxicityJ Dairy Sci.(2011 Aug)
  12. ^Hossam Ebaid, Amir Salem, Abdalla Sayed, Ali MetwalliWhey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic ratsLipids Health Dis.(2011 Dec 14)
  13. ^Efthalia Kerasioti, Dimitrios Stagos, Athanasios Jamurtas, Alexandra Kiskini, Yiannis Koutedakis, Nikos Goutzourelas, Spyros Pournaras, Aristidis M Tsatsakis, Dimitrios KouretasAnti-inflammatory effects of a special carbohydrate-whey protein cake after exhaustive cycling in humansFood Chem Toxicol.(2013 Nov)
  14. ^Gøran Paulsen, Kristoffer T Cumming, Geir Holden, Jostein Hallén, Bent Ronny Rønnestad, Ole Sveen, Arne Skaug, Ingvild Paur, Nasser E Bastani, Hege Nymo Østgaard, Charlotte Buer, Magnus Midttun, Fredrik Freuchen, Havard Wiig, Elisabeth Tallaksen Ulseth, Ina Garthe, Rune Blomhoff, Haakon B Benestad, Truls RaastadVitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trialJ Physiol.(2014 Apr 15)
  15. ^Tom Clifford, Owen Jeffries, Emma J Stevenson, Kelly A Bowden DaviesThe effects of vitamin C and E on exercise-induced physiological adaptations: a systematic review and Meta-analysis of randomized controlled trialsCrit Rev Food Sci Nutr.(2020)
  16. ^Cristina Canals-Garzón, Rafael Guisado-Barrilao, Darío Martínez-García, Ignacio Jesús Chirosa-Ríos, Daniel Jerez-Mayorga, Isabel María Guisado-RequenaEffect of Antioxidant Supplementation on Markers of Oxidative Stress and Muscle Damage after Strength Exercise: A Systematic ReviewInt J Environ Res Public Health.(2022 Feb 5)
  17. ^Mayur K Ranchordas, David Rogerson, Hora Soltani, Joseph T CostelloAntioxidants for preventing and reducing muscle soreness after exercise: a Cochrane systematic reviewBr J Sports Med.(2020 Jan)