Cross-Education of Strength: From Theory to Practice in Contemporary Sports Rehabilitation—A Narrative Review and Clinical Implications

Abstract

Background

Cross-education (CE) of strength refers to strength gains in the untrained limb after unilateral resistance training. Despite the long-standing recognition of this phenomenon, its potential implications in clinical and rehabilitation settings have only been studied extensively in recent decades.

Main body

The implementation of unilateral resistance training in early-stage sports rehabilitation remains underrated, likely due to the lack of consensus on evidence-based guidelines. Thus, this narrative review provides a current overview of the CE of strength, analyzes its practical implications for sports rehabilitation, and examines the training modalities and parameters that should be modulated to optimize CE adaptations, thereby supporting early intervention against post-injury neuromuscular decline.

Conclusions

Unilateral resistance training in the healthy limb appears to represent a cost-effective and accessible rehabilitation strategy for athletes who are unable to work on their injured limb from the early stages of rehabilitation. This strategy may ensure the maintenance of muscle strength levels in the trained limb while minimizing neuromuscular decline in the injured and immobilized limb. CE of strength may be implemented as an addition to traditional early-stage rehabilitation strategies, such as pain, swelling, and inflammation reduction, the progressive restoration of joint range of motion, and the progressive strength training in sports injury rehabilitation. Further research is required to make definitive recommendations.

Key Points

Strength gains in the untrained limb following unilateral resistance training is a phenomenon known as cross-education (CE), with origins tracing back to the second half of the 19th century.

In sports rehabilitation, it is essential to promptly address the negative effects of injury, immobilization, and detraining starting from the early stages to optimize later rehabilitation phases.

Despite the lack of consensus, CE of strength may be a promising strategy in early-stage sports rehabilitation to preserve the neuromuscular function of the injured area. This approach relies on the precise modulation of training parameters, which is critically discussed in this article.

Background

Cross-education (CE) of strength refers to strength gains in the untrained limb after unilateral resistance training [1]. In recent decades, the growing interest in the potential benefits of unilateral resistance training, particularly in clinical-rehabilitative scenarios, has led to a substantial increase in the number of articles focused on the CE effect [2–4]. Although interest in this phenomenon has grown in recent years, its origins date back to the 19th century [5].

The terminology used to describe its effects has become increasingly heterogeneous: “cross-transfer”, “cross-effect”, “cross-training”, and “inter-limb transfer” [6]. Nonetheless, the term most commonly used in the scientific literature in reference to unilateral strength training remains “cross-education” [7, 8].

Previously, the existence of this phenomenon was widely questioned [9], seeking to justify whether it represented a physiological improvement or simply an artifact derived from familiarization with experimental procedures and/or inadequate experimental protocols. To date, the existence of the CE effect has been proven by several meta-analyses [4, 10–14], highlighting moderate to large contralateral strength gains [10], varying based on the type of muscle contraction and the modulation of training parameters in the prescription of resistance training [8], the characteristics of the reference population [12], and the different inter-individual responsiveness [15].

In addition to promoting strength gains in the untrained limb under healthy conditions [4, 9, 16], the CE effect may also attenuate strength loss in the injured limb [2, 17–20], potentially counteracting the muscle atrophy associated with immobilization [18, 21–25], as further supported by a previous systematic review and meta-analysis [13].

Despite the demonstrated clinical efficacy of the CE effect [2, 23, 26], unilateral resistance training remains infrequently and inconsistently prescribed [27]. This disconnect may be largely attributed to the absence of shared, evidence-based guidelines that translate experimental findings into practical, actionable protocols. Existing reviews and meta-analyses [4, 8, 11–13, 23, 28, 29] often lack an integrated evaluation of key training variables, such as volume, intensity, contraction type, frequency, dose-response relationships, as well as the effects of different training modalities. This represents a critical yet overlooked aspect, given the well-known central role these variables play in eliciting specific stimuli and neuromuscular adaptations to resistance training [30–37].

Consequently, there is limited guidance on how to effectively optimize the CE of strength through targeted program design, as reflected by the heterogeneous methodologies employed in current research. The literature also fails to critically integrate mechanistic knowledge with applied outcomes, leaving a persistent gap between theory and practice. These limitations highlight the need for a comprehensive, narrative synthesis capable of reframing current evidence, identifying unresolved questions, and outlining future directions for research and application.

Therefore, the purpose of this narrative review is to provide a current overview of the CE of strength, analyze its practical implications for sports rehabilitation, and examine the training modalities and parameters that should be modulated to optimize adaptations, thereby assisting clinicians and practitioners in mitigating post-injury neuromuscular decline from the early stages of sports rehabilitation.

Methods

A retrospective methodology was employed to identify relevant full-text English-language publications that evaluated, applied, or discussed the concept of CE of strength, involving orthopedic clinical and non-clinical conditions and excluding neurological conditions. Literature searches were carried out across PubMed, Web of Science, Scopus and Google Scholar databases up to 30 June 2025.

Studies were included based on their relevance to both the conceptual and applied aspects of CE of strength. Specifically, the inclusion criteria were as follows: (1) the article addressed CE of strength from a mechanistic or practical perspective; (2) the study involved orthopedic clinical (e.g., following muscle-, tendon-, or joint-related injuries) or non-clinical (e.g., healthy individuals undergoing immobilization) contexts; (3) no restrictions were applied concerning training types (e.g., isotonic, isokinetic, free weights, etc.) or modalities (e.g., eccentric training, isometric training, etc.) aimed at enhancing CE of strength, provided that sufficient information was reported regarding key training parameters (e.g., volume, intensity, frequency, progressive overload, etc.); (4) both athlete and non-athlete populations were considered; (5) no restrictions were applied regarding participants’ age, sex, or geographical location; (6) the article was published in English; and (7) the full text was available. The exclusion criteria were as follows: (1) the article did not directly address CE of strength; (2) the article lacked sufficient methodological detail to allow for proper interpretation; and (3) the article focused on neurological clinical conditions.

The initial screening was independently conducted by two reviewers (M.M. and R.C.) in a first-level review. A second-level screening was subsequently carried out by two additional reviewers (F.E. and F.M.I.) to ensure consistency and minimize selection bias.

Main text

Determinants and characteristics of cross-education of strength

The CE effect appears to be mediated by neural adaptations [1, 10, 13, 18, 38–40] rather than muscular ones [41], as evidenced by the absence of significant vascular [42] and histological [9] muscular adaptations.

Among the main theoretical models used to explain the neural determinants underlying the CE effect are the hypotheses of “cross-activation” and “bilateral access” [1]. In the first case, the repeated execution of unilateral motor tasks is associated with increased excitability of ipsilateral and contralateral cortical motor areas, resulting in simultaneous neural adaptations in both cerebral hemispheres. In the second case, the motor engrams elaborated following unilateral training are not exclusive to the trained limb but rather coded in brain centers also accessible to the control of the untrained limb. Additionally, several studies on mirror neurons have analyzed how the mere visualization of a movement can provoke adaptation [43–45], potentially modifying the CE effect. Others have examined the ability of unilateral resistance training to produce interhemispheric plasticity [3].

Notably, the work of Ruddy and Carson [1] has provided valuable insights into the role of interhemispheric interactions and functional connectivity in modulating the CE effect, suggesting that alterations in transcallosal inhibition may be a key neural mechanism underlying performance enhancements in the untrained limb. Specifically, changes in transcallosal inhibition, a mechanism by which one hemisphere exerts inhibitory control over the other via the corpus callosum, may facilitate the interhemispheric transfer of motor gains.

Recent findings have further highlighted the pivotal role of specific corpus callosum subregions, such as the rostral body, in mediating CE of strength [46], thereby advancing current understanding of how callosal microstructure supports the interhemispheric dynamics underpinning CE.

These findings indicate that the neural adaptations associated with unilateral motor training are not confined to the primary motor cortex contralateral to the trained limb, as illustrated by Hendy et al. [39], but also involve dynamic changes in both hemispheres [47], including alterations in the temporal lobe [16, 43, 48]. In particular, Farthing et al. [48] demonstrated increased activity in the ipsilateral temporal lobe during isometric contractions of the untrained limb following unilateral training, using functional magnetic resonance imaging. This suggests that CE may engage higher-order integrative regions, such as those in the temporal lobe, which are potentially involved in multisensory processing, motor imagery, or the consolidation of motor memory. These findings broaden the scope of neural substrates implicated in CE, moving beyond the classical motor pathways and highlighting a more distributed network of neuroplastic changes.

Consistently, significant reductions in cortical inhibitory mechanisms have also been observed, suggesting that inhibitory processes within the ipsilateral primary motor cortex may modulate corticospinal excitability in the untrained hemisphere following chronic contralateral training [10]. In this context, interactions between GABAergic intracortical circuits, such as those mediating short-interval intracortical inhibition and the cortical silent period, are likely to contribute to the observed adaptations in corticospinal output to the untrained muscles [10].

Altogether, these converging mechanisms support the view that interhemispheric plasticity, rather than localized cortical adaptations alone, plays a fundamental role in CE, particularly in tasks involving strength development and motor skill acquisition.

Moreover, it appears that the amount of “cross-facilitation” is positively correlated with the amount of force generated by the contraction of the trained limb [49, 50]. This result suggests an intensity-dependent relationship if the goal is to maximize adaptations. In support of this, it was recently shown that the CE effect occurs following high-intensity unilateral resistance training (i.e., 75% of one repetition maximum, 1RM), but not after low-intensity training (i.e., 25% 1RM [51]), highlighting the critical role of load in driving neuromuscular adaptations. Furthermore, the extent of strength transfer in the untrained limb appears to be proportional to the strength gains achieved in the trained limb [25, 44, 52].

In light of this, the absence of voluntary neural drive (e.g., passive mobilization of a limb) could be a limiting factor for the CE effect. Indeed, adaptations can be detected in circumstances where the output circuits of the primary motor cortex receive a synaptic impulse, such as during voluntary contractions [53]. Therefore, unilateral resistance training can increase the motor cortex’s ability to drive the contralateral untrained muscles [54].

However, significant contralateral strength gains have been observed following muscle electrostimulation [12, 55, 56]. This result has significant practical relevance, especially in the immediate post-injury phases where motor intervention may not yet be well tolerated for several reasons (e.g., athlete compliance), even if on the contralateral side to the injured side.

Alternatively, unilateral eccentric training in the ipsilateral lower/upper limb to the injured upper/lower limb results in neuromuscular adaptations (e.g., maximal strength, voluntary muscle activation, power) on the contralateral side [57–59]. Therefore, in the presence of a disabling injury to a segmental area (e.g., right lower limb), training the other ipsilateral segmental area (e.g., right upper limb) could ensure neuromuscular adaptations benefiting the injured area.

An interesting question is whether the CE effect can be sought acutely and persist beyond the training period. Greater corticospinal excitability and contralateral strength gains have been highlighted both acutely [37, 60] and chronically [61–63]. Recently, it has also been shown in clinical settings that following 4 weeks of unilateral resistance training in the healthy limb, significant muscle strength increases in the knee extensor and neuromuscular function in the opposite limb with osteoarthritis were maintained up to 3 months after the intervention period [64]. This suggests that CE may induce durable adaptations in the untrained limb, with potential to support recovery throughout the continuum of rehabilitation.

Significant contralateral strength gains have been observed both in the upper limb (+ 28.1% [53]; +19.2% [65]; +13.7% [66]; +12.5% [67]) and in the lower limb (+ 33% [6]; +17.8% [68]; +20.4% [69]; +35% [70]; +15% [71]; +22.7% [72]; +23.4% [73]). Despite recent conflicting results [12], greater adaptive responses appear to involve the lower limb muscles [4]. However, this divergence could be attributed to several factors, including: methodological differences (e.g., type and level of muscle contraction) in the prescription of resistance training; neuroanatomical and functional differences between upper and lower limbs, as the neural control of lower limbs involves more bilateral and integrative circuits [74]; the predominance of daily symmetrical functional tasks (e.g., locomotion) in the lower limbs compared to the often unilateral use of upper limbs; and variations in habitual use and individual motor experience.

Nevertheless, the magnitude of strength transfer appears to be more variable in the upper limb compared to what is observed in the lower limb, where contralateral gains are uniform across different muscle groups and contraction modalities [4]. The reason for this disparity could lie in the different ability to voluntarily contract the upper and lower limb muscles.

Regarding the CE effect across different muscle groups, training distal rather than proximal muscle groups, irrespective of the body region, does not appear to produce significantly different magnitudes of CE [64], as supported by a prior meta-analysis conducted by Manca et al. [4]. However, when distal and proximal muscle groups are compared across body regions (i.e., upper vs. lower limb), a trend toward greater contralateral strength gains has been observed for distal muscles in the upper limb only [4]. In this context, when the clinical conditions affect proximal regions of the upper limb (e.g., following anterior shoulder stabilization surgery), clinicians may need to implement specific strategies to enhance contralateral transfer in these muscle groups. Such strategies could include combining high-intensity unilateral strength training with adjunct techniques that are feasible in day-to-day practice such as mirror therapy [43–45], or non-invasive neuromodulatory approaches such as transcranial direct current stimulation [38, 75, 76].

In this regard, although the application of neuromodulation in sports could raise ethical concerns, it is important to note that, unlike pharmacological interventions, these techniques do not involve the introduction of exogenous substances. Nonetheless, further research is needed before they can be formally recommended, particularly regarding appropriate regulation in competitive settings, potential side effects (e.g., athlete harm or altered performance), their influence on neural plasticity and synaptogenesis, and the uncertainty surrounding the duration of their effects [77]. Given the current lack of robust consensus, the use of such techniques in sports rehabilitation cannot yet be recommended.

Recently, it has been shown that the CE effect is site-specific and movement-specific [18, 78]. Therefore, from a practical standpoint, multiple exercises and movements may be necessary if several muscle groups are affected/immobilized following an injury, favouring exercises with which the athlete is more familiar [48, 79]. Recent evidence also suggests that CE effect is context-dependent [80, 81]. Specifically, Bell et al. [80] found that unilateral high-load training enhances strength in the contralateral limb even when that limb performs low-load exercise. Conversely, Song et al. [81] demonstrated that while CE occurs with unilateral high-load training, it does not further increase strength when the contralateral limb is concurrently trained at high load, indicating non-additivity in bilateral high-load protocols. These findings support rehabilitation strategies in which the injured or weaker limb is restricted to low-intensity exercise, while the healthy limb undergoes high-intensity training to maximize recovery through CE [80]. However, when both limbs train at high intensity, CE offers no additional strength benefit [81], suggesting its effects are context-dependent and most relevant in asymmetrical training or rehabilitation settings.

Finally, contrary to what was hypothesized [82], recent studies have shown that the magnitude of the CE effect does not appear to decrease with age [83, 84] and that it can also be elicited in elderly individuals to mitigate strength and dexterity decline [85]. These results are consistent with previous observations [3, 7], as well as the meta-analysis conducted by Green et al. [12]. Since in sports settings, particularly in team sports, the same team can be composed of athletes of heterogeneous ages, this would not be a limiting factor if the objective of a given rehabilitation session was to seek the CE effect.

Cross-education of strength in sports rehabilitation

Unilateral injuries are extremely common in sports and can result in days, weeks, or months of immobilization of the affected limb. The time away from training and competition can lead to detrimental effects on muscle strength and endurance [86]. In such circumstances, the ability to preserve muscle strength and neural adaptations is of particular prognostic importance [87], as it can potentially facilitate an earlier return to sports practice and daily activities compared to traditional rehabilitation protocols [2, 17, 20]. In recent decades, among the promising strategies investigated to achieve this goal is the CE of strength [13, 19, 29, 88–91], as additionally reinforced by an overview of Cochrane systematic reviews [92]. Thus, its potential benefits in sports rehabilitation warrant further investigation.

Scientific research on limb immobilization has traditionally focused on intramuscular effects [93–96]. In particular, the absence of mechanical stimulation results in disuse muscle atrophy [93], with significant morpho-functional changes evident as early as the first week of immobilization [97]. However, the nervous system is also impacted [98–101]. In relatively early stages, limb immobilization leads to a decrease in the excitability of cortical motor areas [102, 103], voluntary muscle activation [10, 22, 101], and maximal force production capacity [2].

Recently, the implementation of the CE effect for rehabilitative purposes has been contested [104], due to the potential risk of increasing asymmetries in muscle trophism between the healthy and injured limbs. However, modulating training parameters, such as volume and intensity, in resistance training prescriptions is essential to elicit predominantly neural rather than peripheral adaptations [105]. Thus, this approach may help minimize time under tension and metabolic stress on the target muscle group, as these stimuli promote hypertrophy and greater fatigue [106, 107].

The advantage of preserving the neuromuscular function of the injured area from the early stages of rehabilitation through the CE effect may help mitigate the degenerative processes previously examined, minimizing the decline in muscle strength and the extent of side-to-side asymmetries [3, 17, 19, 20, 29], which can be corrected later (e.g., when it becomes possible to work directly on the injured limb).

Therefore, the implementation of the CE effect would represent an additional intervention in early-stage rehabilitation [17, 19, 88, 91], alongside the reduction of pain, swelling, inflammation, and the progressive restoration of joint range of motion in the injured limb [108]. Consequently, this implementation should not be mistakenly viewed as a substitute for the progressive strength training required in the rehabilitation of sports injuries, such as anterior cruciate ligament reconstruction (ACLr [109]).

It is well known that from the early stages of post-injury rehabilitation, mitigating the decline in muscle strength to achieve progressive functional capacity in both limbs represents a clinically significant outcome, given that strength deficits are often observed bilaterally following particularly debilitating unilateral injuries [108–110].

For example, quadriceps weakness following ACLr has been associated with arthrogenic muscle inhibition [108, 111, 112], reduced voluntary activation consequent to surgery [113], increased excitability of reflex spinal pathways and decreased excitability of corticospinal pathways [114], as well as muscle atrophy [115]. In these circumstances, the implementation of rehabilitation strategies capable of minimizing these deleterious effects would be of great clinical relevance [19, 24, 116]. Since the CE effect appears to fulfill this purpose [20, 88], it may represent a viable rehabilitation strategy to minimize the extent of neuromuscular deconditioning in the early stage, preserving strength and potentially muscle trophism during the period of orthopedic immobilization [13, 18, 21, 22, 24, 25, 117–119].

These findings align with a recent systematic review and meta-analysis [29], which, despite the limited number of studies included (a major limitation), reported moderate to high-quality evidence and statistically significant effects, indicating that adding unilateral strength training to standard rehabilitation enhances quadriceps strength in the injured limb following ACLr.

Finally, the ability to maximize quadriceps strength in the healthy limb while preserving strength in the injured limb represents an essential component in the rehabilitation of particularly debilitating injuries such as ACLr [20, 120]. Nevertheless, further studies on the CE effect in clinical-rehabilitation scenarios are still necessary to address the divergence in results [2, 17, 20, 121, 122], likely attributable to the various methodological and contextual aspects to be considered in the prescription of unilateral resistance training, many of which are critically analyzed and discussed in the present review.

In this regard, given that the CE of strength relies on neural mechanisms [10], the modulation of training variables in unilateral strength training should follow specific principles, such as high intensity, low repetitions, and full recovery between sets [123]. Failure to reach sufficient load intensity (e.g., 8-12RM [121, 122] vs. 90% 1RM [16] or 3-5RM [20]) may limit the neuromuscular adaptations necessary to optimize the CE effect, as suggested by the randomized controlled trials conducted by Zult and colleagues [121, 122]. In contrast, when training parameters, particularly load intensity, are appropriately prescribed across both single-joint and multi-joint exercises, high-intensity CE-based strength training has been shown to attenuate the effects of detraining in the weaker arm [16] and postoperative quadriceps strength loss following ACLr [20], thereby supporting its implementation in early-phase rehabilitation protocols.

Moreover, with regard to the relevance of high-intensity loading, the findings of our review align with the recommendations recently outlined in the review by Buckthorpe et al. [124] and the Delphi study by Manca et al. [125], which underscore not only the critical role of intensity in maximizing training efficacy but also the importance of incorporating CE as an adjunctive strategy in early-stage rehabilitation, as previously discussed. This is particularly pertinent in the management of unilateral orthopedic conditions and sports injuries, where CE may offer a valuable neural stimulus to preserve strength in the injured limb during periods of immobilization.

Given the therapeutic potential of CE of strength, there is a clear need for a principled framework to guide the design of interventions and to tailor them to individual needs, as critically discussed below.

Modulation of training parameters

Frequency

Two weeks of unilateral resistance training (2 sessions/week) have been considered insufficient to produce significant contralateral strength gains in the upper limb [126]. Contrary to this, prescribing at least 2–4 weeks (3 sessions/week) appears to be the minimum time required for adaptations related to the CE effect [73, 76, 127–129]. Given the neural determinants potentially underlying this phenomenon, the aforementioned results are not surprising, as the minimum period for the initial nervous system adaptations following resistance training is approximately 4 weeks [130]. However, unlike purely peripheral-muscular adaptations, neuromuscular adaptations in response to training occur earlier [131].

Finally, a higher training frequency (≥ 5 sessions/week vs. 3 sessions/week) does not appear to result in greater adaptations [17, 88, 129, 132], but it does increase the rate at which adaptations occur, with similar contralateral strength gains achieved in half the time [129].

Intensity

Resistance training intensity is undoubtedly the most important variable for achieving neural adaptations [133]. Several studies have examined the role of training intensity in the CE effect, evaluating handgrip [134, 135], elbow flexion [136, 137], unilateral leg press [58, 62], and knee extension strength [51]. Overall, the results suggest that greater contralateral strength gains are obtained by working at high intensities compared to low intensities (e.g., ≥ 80% 1RM vs. ≤ 40% 1RM or 5RM vs. 20RM).

Nevertheless, another factor potentially influencing contralateral strength gains appears to be the development of fatigue during unilateral muscle contractions [28, 50, 138]. Contrary to previous findings [51], training protocols inducing greater muscle fatigue, even at moderate-low intensities, could elicit CE of strength [139, 140]. This result may not be surprising, as muscle failure during low-intensity resistance training corresponds to greater motor unit recruitment [141], neural adaptations and strength gains [142, 143]. From a practical standpoint, low-intensity training to muscle failure could represent an alternative for achieving the CE effect in athletes unable to tolerate high-intensity training (e.g., due to comorbidities), albeit in the contralateral limb to the injured one. However, early contralateral strength gains appear to be obtained by favouring high-intensity unilateral resistance training (e.g., 80% 1RM vs. 40% 1RM [137]). Finally, for several reasons, muscle failure training is not recommended for prolonged periods [144], including the potential risk of increasing asymmetry in muscle trophism between the healthy and injured limb in clinical-rehabilitation scenarios [104], due to an increase of muscle protein synthesis [145].

Volume

A minimum of 13–18 sessions is necessary to maximize the CE effect [125, 129]. Regarding the number of sets, prescribing 3 sets versus a single set during unilateral resistance training ensures greater contralateral strength gains [52]. Concerning the number of repetitions, although the exercise is prescribed at high intensity (e.g., 90% 1RM), low volume (e.g., 5 sets of one single repetition) does not appear to produce significant adaptations [146].

Less strenuous training programs, characterized by moderate volume and adequate recovery between sets, have been shown to elicit greater adaptations compared to more strenuous workouts characterized by sets to muscle failure [11].

Overall, traditional configurations of high-intensity strength training volume (i.e., >1 set of < 8 repetitions) produce the most robust adaptations related to the CE effect [147].

Muscle contraction pattern

Several methodological variables appear to be capable of modifying the adaptations of the untrained limb following unilateral resistance training [11, 51], including the muscle contraction pattern.

Although the magnitude of the CE effect differs based on the type of muscle contraction (8.2% isometric, 11.3% concentric, 17.7% eccentric, 15.9% isotonic-dynamic [4]; 24.9% isoinertial [25]), all modalities significantly increase contralateral strength [4, 8, 148]. Consequently, it is possible that the CE effect may be pursued in various ways and contexts during different phases of sports rehabilitation, for example through interventions that progressively transition from static (e.g., isometric) to dynamic (e.g., eccentric, concentric-eccentric) strength regimes.

To date, several studies on the CE effect have focused on isometric or exclusively concentric training [4, 9, 149]. However, compared to concentric contractions, eccentric contractions provide a potent stimulus for strength increases in both the trained and untrained limbs [8, 90, 118, 150–154]. Indeed, the combined effect of dynamic contractions (e.g., concentric-eccentric) appears to guarantee greater adaptive responses related to the CE of strength [4, 8]. Additionally, compared to concentric training, low-load eccentric training with blood flow restriction (i.e., simultaneous restriction of blood flow to and from the contracting muscles [155]) also appears to ensure greater contralateral strength gains [156]. It was also observed that incorporating blood flow restriction into low-intensity isometric training resulted in a significantly greater CE effect on isometric strength compared to other experimental groups, including high-intensity isometric training [157].

Overall, the main adaptations following high-load unilateral resistance training and/or predominantly eccentric exercises could be attributed to increased hemisphere activation of the untrained limb and reduced cortical inhibitions [40, 153]. Additionally, greater corticospinal excitability has been observed during eccentric contractions compared to concentric contractions [158], except in the acute post-exercise phase, where Valdes et al. [37] reported a reduction following eccentric training. Nevertheless, their findings [37] confirm that eccentric training elicits a stronger acute CE effect than concentric training, suggesting that mechanisms beyond corticospinal excitability (possibly spinal or peripheral) may contribute to early contralateral strength gains. These results indicate that, under time-constrained conditions (e.g., in high-performance sports scenarios), eccentric (or combined) contractions may still represent the preferred strategy to rapidly induce CE effects.

Finally, it has been demonstrated that the repeated bout effect (i.e., adaptation where repeated exposure to eccentric exercise protects against muscle damage from subsequent exposures [159]) may also transfer to the untrained limb [154, 160, 161]. This finding holds considerable practical relevance, as it suggests that eccentric conditioning of the healthy limb (e.g., via strategies such as tempo eccentric training [162]) may enhance the injured limb’s tolerance to eccentric loading during the later stages of rehabilitation, once direct training becomes feasible.

Nevertheless, the benefits derived from the CE effect are likely to depend on several factors, including the mode of muscle contraction utilized (with contraction-specific adaptation patterns [63]), the reference population, predefined goals, and individual characteristics. For instance, the relevance of eccentric contraction might be even more pronounced in soccer players recovering from hamstring injuries [163], hamstring tendon repair [164] or following ACLr using a hamstring autograft [108, 165]. In such cases, unilateral eccentric strength training could not only help maintain strength levels in the healthy limb (used as a reference during rehabilitation [166]) and promote structural adaptations beneficial to performance and injury risk reduction, such as fascicle length [163, 167], but could also simultaneously attenuate the decline in (eccentric) strength in the injured limb and transfer the repeated bout effect to it, as previously discussed.

Recent findings related to ankle plantarflexor strength support this, demonstrating that a 6-week isokinetic eccentric training program led to significant increases in isometric and eccentric peak plantarflexor torques in both the trained and untrained limbs, along with improvements in dorsiflexion range of motion, stretch tolerance, and passive elastic energy storage [168].

Conclusions

Unilateral resistance training in the healthy limb appears to represent a cost-effective and accessible rehabilitation strategy for athletes who are unable to work on their injured limb from the early stages of rehabilitation. This strategy may ensure the maintenance of muscle strength levels in the trained limb while minimizing neuromuscular decline in the injured and immobilized limb. The underlying phenomenon of this condition is identified as the CE effect, which may be implemented as an addition, rather than a replacement, to traditional early-stage rehabilitation strategies (such as pain, swelling, and inflammation reduction, and the progressive restoration of joint range of motion) and the progressive strength training in sports injury rehabilitation. Further research is required to make definitive recommendations. Table 1 provides a practical and ecological framework for applying unilateral resistance training to enhance the CE of strength.

Table 1.

Practical overview of unilateral resistance training for enhancing the CE of strength

Training parameter	Recommendation	Reference
Frequency	≥ 3 sessions/week for >2–4 weeks	[73, 76], 127– [129]
Intensity and muscle contraction pattern	>80% of maximum voluntary isometric contraction in a static regime (e.g., isometric) or >80% of 1RM in a dynamic regime (e.g., eccentric-concentric)	[16, 20, 51, 58, 62, 123, 125], 134– [137]
Volume	>1 set for < 8 reps (e.g., 3–4 reps for 3–4 sets)	[11, 123, 147]
Rest	Full rest (e.g., 3 min)	[11, 123]
Exercise	Both single-joint (e.g., leg extension) and multi-joint (e.g., leg press) exercises, as long as familiar to the athlete	[20, 48, 79]

1RM one repetition maximum, reps repetitions

Limitations and future perspectives

Most studies conducted on the CE effect have reported within-group designs, lacking a control group of subjects not subjected to the experimental intervention [9, 149]. Additionally, the research has primarily analyzed healthy individuals subjected to immobilization. Consequently, further randomized controlled clinical trials that account for the insights and findings highlighted in this review are necessary to develop definitive recommendations applicable to clinical practice.

Future studies should better control potential confounding variables that could influence contralateral strength gains: the dominance of the trained limb, as greater effects are observed when the dominant limb corresponds to the trained limb [3], although recent conflicting results exist [67, 169–171]; the high risk of error related to the procedures used to determine participants’ laterality [66, 68, 79, 152]; the training status of the participants and their competitive level; the functional and/or clinical relevance of contralateral strength gains [52, 54, 172]; and the use and description of preliminary familiarization procedures [4], which, if omitted, may lead to an overestimation of contralateral strength gains [173].

Moreover, the methods used to test muscle strength have been heterogeneous. Some studies have conducted evaluations using isometric or isokinetic dynamometers, mixed methods, or the 1RM method [4]. Therefore, greater standardization of experimental procedures would be desirable for a consensual interpretation of results across different studies.

Additionally, future scientific investigations should adopt a consensual nomenclature when referring to contralateral strength gains following unilateral strength training. In light of the above, it would be appropriate to indicate this phenomenon with the original term “cross-education” [7, 8]. A consensual nomenclature would facilitate the acquisition of scientific resources and the conduct of future systematic reviews and/or meta-analyses with larger sample sizes.

Finally, future studies on the CE effect should ensure that the untrained limb remains completely relaxed during unilateral training, as even low-level activation could induce strength gains [10].

Overall, although the transfer of contralateral strength due to the CE effect has been extensively examined, a recent systematic review and meta-analysis find little support for the benefit of this outcome [174]. While the existence of the phenomenon is not denied [174], the study emphasizes the need for further research that addresses the previously examined limitations.

Abbreviations

CE

Cross education

1RM

One repetition maximum

ACLr

Anterior cruciate ligament reconstruction

Author contributions

M.M. was responsible for the original idea of the manuscript; contributed to the conception and design of the study and the acquisition, analysis, and interpretation of data; drafted the article and critically revised it for important intellectual content. R.C. contributed to the conception and design of the study and the acquisition, analysis, and interpretation of data; drafted the article and critically revised it. F.E. drafted the article and critically revised it for important intellectual content. F.M.I. read the manuscript and provided important intellectual contributions to the original draft and revisions. All authors approved the submitted version.

Funding

No funding was received for conducting this study.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

As the information of this study are publicly accessible, no ethics approval was required. Data included in this study were extracted from prior studies that obtained written prior consent for publication.

Consent for publication

Not applicable.

Competing interests

Mauro Mirto, Fabio Esposito, F. Marcello Iaia and Roberto Codella declare that they have no financial, personal, or professional conflicts of interest related to this work.