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Review
. 2025 May 27;15(6):867.
doi: 10.3390/life15060867.

The 4Rs Framework of Sports Nutrition: An Update with Recommendations to Evaluate Allostatic Load in Athletes

Diego A Bonilla  1   2   3 , Jeffrey R Stout  4 , Michael Gleeson  5 , Bill I Campbell  6 , Guillermo Escalante  7 , Daniel Rojas-Valverde  8   9 , Jorge L Petro  1   10 , Richard B Kreider  11 , Adrián Odriozola-Martínez  2
Affiliations
Review

The 4Rs Framework of Sports Nutrition: An Update with Recommendations to Evaluate Allostatic Load in Athletes

Diego A Bonilla et al. Life (Basel). .

Abstract

The 4Rs of sports nutrition were proposed in recent years as an evidence-based framework to optimize post-exercise recovery within the context of allostasis. Under this paradigm, it is important to consider that each R represents a factor with a tremendous influence on the allostatic response and improves individual components of the allostatic load (AL), which will positively impact the exercise-induced adaptations and the athlete's recovery. The 4Rs correspond to the following. (i) Rehydration-This is necessary to guarantee the post-exercise consumption of at least 150% of the body mass lost during the exercise accompanied by sodium (if faster replacement is required). (ii) Refuel-Carbohydrate intake (~1.2 g/kg body mass per hour for up to 4 h post-exercise) is essential not only in restoring glycogen reserves but also in supporting the energy needs of the immune system and facilitating tissue repair. Despite changes in substrate utilization, a ketogenic diet generally has neutral or negative effects on athletic performance compared to carbohydrate-rich diets. (iii) Repair-The ingestion of high-quality protein stimulates post-exercise net muscle protein anabolism and might contribute to faster tissue growth and repair. The use of certain supplements, such as creatine monohydrate, might help to enhance recovery, while tart cherry, omega-3 fatty acids, and dietary nitrate (e.g., Beta vulgaris, Amaranthus L.), as well as other herbal extracts containing flavonoid-rich polyphenols, deserve further clinical research. (iv) Recuperate-Pre-sleep nutrition (casein- or protein-rich meal with slow digestion rate) has a restorative effect, facilitating the recovery of the musculoskeletal, endocrine, immune, and nervous systems. In this article, we update the 4Rs framework, delve deeper into the allostasis paradigm, and offer theoretical foundations and practical recommendations (the 4Rs app) for the assessment of AL in athletes. We cautiously propose an AL index (ALindex) for physique competitors and elite athletes to evaluate the cumulative physiological stress induced by exercise and, thereby, to adjust exercise and nutrition interventions.

Keywords: allostasis; biomarkers; cacostasis; physiological adaptation; sports nutritional sciences.

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Conflict of interest statement

D.A.B. serves as the scientific and managing director of KreaFood, an R&D&I Project; has served as the science product manager for the MTX Corporation® in Europe; has acted as a scientific consultant for MET-Rx® and Healthy Sports in Colombia; has conducted academic-sponsored research on nutritional supplements; and receives honoraria for speaking about sports nutrition at international conferences and private courses. R.B.K. has conducted industry-sponsored research on dietary supplements; received financial support for presentations about dietary supplements at industry-sponsored scientific conferences; and has served as an expert witness on cases related to exercise, nutrition, and dietary supplementation. B.I.C. has received grants and contracts to conduct research on dietary supplements; has served as a paid consultant for industry; has received honoraria for speaking at conferences and writing lay articles about sports nutrition ingredients and topics; and has served as an expert witness on cases involving dietary supplements. G.E. serves on the Scientific Advisory Board and as the lead Physique and Bodybuilding Program subject matter expert for the National Academy of Sports Medicine; he has also served as a paid scientific consultant for various dietary supplement companies. J.R.S. has conducted industry-sponsored research on sports nutrition over the past 25 years. Further, J.R.S. has also received financial support for presenting on the science of various nutraceuticals, at industry-sponsored scientific conferences. M.G. has received grants and contracts to conduct research on sport nutrition products and dietary supplements; has served as a paid consultant for industry; and has received honoraria for speaking at conferences and writing lay articles about sports nutrition ingredients and topics. Finally, R.B.K. serves as Chair of the “Creatine for Health” scientific advisory board sponsored by Creapure® and Creavitalis®—Alzchem Group AG, while D.A.B., B.I.C., and J.R.S. serve as members of this board. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The 4Rs framework of sports nutrition. Source: designed by the authors (D.A.B.).
Figure 2
Figure 2
The time course of exercise-induced adaptation. Transient changes in metabolite sensing and signaling during/after exercise drive the gene transcription of early genes; myogenic regulators; genes of carbohydrate metabolism, lipid mobilization, transport and oxidation, mitochondrial metabolism, and oxidative phosphorylation; and transcriptional regulators of gene expression and mitochondrial biogenesis. Source: designed by the authors (D.A.B.). Refer to Bonilla et al. (2020) [1] for further information.
Figure 3
Figure 3
Performance-related response of an athlete to chronic physical exercise-induced stress stimuli over time. The color gradient visually represents the transition from optimal adaptation (green) to excessive stress (red). Source: designed by the authors (D.A.B.).
Figure 4
Figure 4
An integrative view of the multifactorial nature of the injury risk in athletes. (A) General features of the allostasis–interoception process. While allostasis represents the adaptive process of stability through change, interoception refers to encoding representations of the internal (physiological) state of the body [85]. (B) Modulation of endogenous pain. Nociplastic pain conditions include the combination of central and peripheral pain sensitization, hyper-responsiveness to painful and non-painful sensory stimuli, and associated features (fatigue, sleep, and cognitive disturbances) [86]. (C) Detailed representation of the allostatic–interoceptive control (as a closed-loop system) of the human body in response to any stimuli. The injury or pain etiology might be discussed in terms of the role of the input signal (stimuli—distal physiology or external world), receptors (sensory surfaces, biological receptors), transmitters (spinal cord, anatomy trains), decoders (central nervous system), regulator elements (autonomic nervous system), and output signal (response, physiological effects). This block diagram was taken from Sennesh et al. (2022) [71]. (D) Schematic illustration of the allodynamic response to stress in sports injuries. AL: allostatic load; HPA: hypothalamic–pituitary–adrenal axis. Source: designed by the authors (D.A.B.). Refer to Bonilla et al. (2022) [2].
Figure 5
Figure 5
Comprehensive approach to biomarker analysis. Reproduced from Lee et al. (2017) [90]—Creative Commons Attribution 4.0 International License.
Figure 6
Figure 6
Immune-related response of an athlete during a time course of chronic stress stimuli in sports. Source: designed by the authors (D.A.B.). Refer to Bonilla et al. (2022) [83].
Figure 7
Figure 7
Athlete Health and Readiness Checklist (AHaRC), providing a multidimensional decision tree to maintain athletes’ health and performance. AH: ad hoc; D: daily; M: monthly; OI: on indication; W: weekly. Reproduced from Jeukendrup et al. (2024) [95]; refer to this for more details related to the AHaRC tool—Creative Commons Attribution 4.0 International License.
Figure 8
Figure 8
Frequency of biomarker use in the allostatic load index. The biomarkers that are shaded in a darker color include the initial ten variables, body mass index, and C-reactive protein. HgbA1C: glycosylated hemoglobin; WBC: white blood cell count; Hgb: hemoglobin. Source: reproduced with permission from Beese et al. (2022) [106].
Figure 9
Figure 9
The 4Rs of sports nutrition and the allostatic load index in athletes. 25(OH)D: total serum 25-hydroxy vitamin D (i.e., the sum of D3 and D2); CHO: carbohydrates; CK: creatine kinase; CRP: C-reactive protein; EA: energy availability; F: female; FFM: fat-free mass; fT/C: free testosterone to cortisol ratio; HRV: heart rate variability; HAMP: hepcidin; b[La−]: blood lactate concentration; M: male; PRO: protein; PUFA ω-3: polyunsaturated fatty acids omega-3; S100B: S100 calcium-binding protein B; sRPE: session rating of perceived exertion. Source: designed by the authors (D.A.B.).
Figure 10
Figure 10
The 4Rs app. Available at https://dbss.shinyapps.io/4RsApp/ (accessed on 22 April 2025). Source: developed by D.A.B.
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References

    1. Bonilla D.A., Perez-Idarraga A., Odriozola-Martinez A., Kreider R.B. The 4R’s Framework of Nutritional Strategies for Post-Exercise Recovery: A Review with Emphasis on New Generation of Carbohydrates. Int. J. Environ. Res. Public Health. 2020;18:103. doi: 10.3390/ijerph18010103. - DOI - PMC - PubMed
    1. Bonilla D.A., Cardozo L.A., Velez-Gutierrez J.M., Arevalo-Rodriguez A., Vargas-Molina S., Stout J.R., Kreider R.B., Petro J.L. Exercise Selection and Common Injuries in Fitness Centers: A Systematic Integrative Review and Practical Recommendations. Int. J. Environ. Res. Public Health. 2022;19:12710. doi: 10.3390/ijerph191912710. - DOI - PMC - PubMed
    1. Lopez-Torres O., Rodriguez-Longobardo C., Escribano-Tabernero R., Fernandez-Elias V.E. Hydration, Hyperthermia, Glycogen, and Recovery: Crucial Factors in Exercise Performance-A Systematic Review and Meta-Analysis. Nutrients. 2023;15:4442. doi: 10.3390/nu15204442. - DOI - PMC - PubMed
    1. Perez-Castillo I.M., Williams J.A., Lopez-Chicharro J., Mihic N., Rueda R., Bouzamondo H., Horswill C.A. Compositional Aspects of Beverages Designed to Promote Hydration Before, During, and After Exercise: Concepts Revisited. Nutrients. 2023;16:17. doi: 10.3390/nu16010017. - DOI - PMC - PubMed
    1. Rowlands D.S., Kopetschny B.H., Badenhorst C.E. The Hydrating Effects of Hypertonic, Isotonic and Hypotonic Sports Drinks and Waters on Central Hydration During Continuous Exercise: A Systematic Meta-Analysis and Perspective. Sports Med. 2022;52:349–375. doi: 10.1007/s40279-021-01558-y. - DOI - PMC - PubMed

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