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Peri-operative protein or amino acid supplementation for total joint arthroplasty: a systematic review and meta-analysis

Abstract

Purpose

Osteoarthritis (OA) affects weight-bearing joints, such as hips and knees, and its prevalence is rising due to factors like obesity and aging. Muscle atrophy, exacerbated by aging and surgery, increases the risk of joint instability and falls. Orthopedic surgeons explore dietary interventions to counteract these effects, with protein supplementation (PS) showing promise. This systematic review and meta-analysis assessed the effectiveness of PS in arthroplasty patients, comparing findings with sports medicine and sarcopenia literature.

Methods

Following PRISMA guidelines, we searched PubMed, Web of Science, Scopus, and Embase (February 2025) for protein and amino acid supplementation studies in total knee or hip arthroplasty (TKA and THA) patients. The quality assessment used the Cochrane risk of bias and the Newcastle–Ottawa Scale. Meta-analysis calculated effect sizes for muscle atrophy and strength outcomes.

Results

Nineteen studies (903 patients) evaluated oral or intravenous protein/amino acid supplementation over a mean follow-up of 55.2 days. Essential amino acids (EAA) significantly reduced muscle atrophy in quadriceps femoris muscle mass (SMD: 0.69; 95% CI: 0.44 to 0.95) and hamstring muscle mass (SMD: 1.04; 95% CI: 0.52 to 1.55). However, effects on intramuscular adipose tissue (IMAT) and muscle thickness (MT) were inconsistent. Muscle strength outcomes varied, with no significant effect on quadriceps muscle strength (QMS) or handgrip strength (HGS). Intravenous amino acid infusion improved muscle protein synthesis and reduced perioperative blood loss.

Conclusions

Protein and amino acid supplementation can reduce muscle atrophy in hip or knee arthroplasty patients. While effects on muscle strength and function are mixed, intravenous supplementation offers benefits. Further standardized research is needed to confirm these findings.

Trial registration

PROSPERO registration code (CRD42024555899).

Background

Osteoarthritis (OA) is the prevailing progressive musculoskeletal disorder primarily impacting weight-bearing joints such as hips and knees. The prevalence of hip and knee OA has witnessed a substantial increase in recent decades and continues to rise. This can be attributed in part to the growing prevalence of obesity and other risk factors, as well as other independent causes [1, 2]. Nevertheless, following total knee arthroplasty (TKA), a considerable number of patients endure pronounced muscle atrophy and weakness, which had been reported to persist for up to 5 months and would compromise balance and functional mobility [3, 4]. Previous reports have indicated that the incidence of postoperative malnutrition can reach as high as 50% after TKA [5] and 40–80% after total hip arthroplasty (THA) [6]. Muscle atrophy is caused by senility and is exacerbated after joint reconstructive surgery [7, 8], which causes increased joint instability and susceptibility to falling. These odds add up to an increase in wear rate, aseptic loosening, periprosthetic fracture, and revision surgeries [9,10,11].

Orthopedic surgeons have shown interest in different dietary and exercise regimens to mitigate this. Among these, protein and amino acid supplementation have become a promising intervention to counteract muscle loss and support postoperative recovery. Protein supplementation (PS) is well-investigated in sports medicine and sarcopenia, where it enhances muscle protein synthesis, preserves muscle mass, and improves strength and function [12,13,14,15,16,17]. Essential amino acids (EAAs), such as leucine, and branched-chain amino acids (BCAAs) are particularly effective due to their role in stimulating anabolic pathways, even in older adults with anabolic resistance [14,15,16,17]. Research suggests older adults benefit from higher protein intakes (e.g., 1.2–1.6 g/kg/day) than the recommended daily allowance (0.8 g/kg/day), especially during catabolic states like surgery [18]. However, 30.3% to 65.1% of older adults with knee or hip OA have daily protein intake below this baseline, highlighting the potential role of supplementation [18]. Beyond quantity, protein quality (defined by EAA content and digestibility) is critical, with options like whey, casein, glutamine, and amino acid infusions (oral or intravenous) showing varying efficacy based on dosage, timing, and administration route [14,15,16,17]. Dietary interventions, including PS, have been integrated into the multidisciplinary approach for managing OA [19, 20].

In this systematic review and meta-analysis, we aim to evaluate the effectiveness of perioperative protein or amino acid supplementation on muscle mass, strength, and functional outcomes in patients undergoing total knee or hip arthroplasty. We compared these findings to established evidence from sports medicine and sarcopenia research to guide clinical practice and future studies.

Material and methods

Protocol and registration

The present systematic review is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The study protocol has been registered in PROSPERO In advance.

Search strategy

We systematically searched medical electronic databases, including PubMed, Web of Science, Scopus, and Embase, in February 2025. We imposed no restrictions and collected all available journal articles up to the search date. A combination of the following keywords was used as a search strategy and narrowed down to title, abstract, and keyword search fields: (“essential amino acid*” OR “glutamine” OR “l-glutamine” OR “branched-chain” OR “BCAA*” OR “albumin infusion” OR “essential amino acid” OR “arginine” OR “l-arginine” OR “amino acid supplementation” OR “amino acid infusion” OR “protein supplementation” OR “protein infusion”) AND (“arthroplasty” OR “hip replacement” OR “knee replacement”).

Eligibility criteria

The population includes patients undergoing knee or hip joint replacement surgery; the intervention was consumption of protein or amino acid supplementation, and the outcome stands for surgical-related complications. Criteria for inclusion encompassed studies (1) involving patients undergoing knee or hip joint arthroplasty, (2) interventions involving oral or injectable protein or amino acid supplementation pre-, intra-, or post-surgery. We excluded case reports, case series, opinions, books, reviews, letters, conference abstracts, in-vivo, and in-vitro studies. Also, we excluded studies in which high-protein diets were used instead of supplements and studies in which the target group had specific diseases affecting protein metabolism.

Study selection

After finalizing the search, duplicates were removed, and the remaining articles were separately screened by two authors (AB and ES) based on title and abstract. The full texts of potentially relevant studies were subjected to a full-text review by two authors (AB and SK), and the first author resolved conflicts. Finally, reference lists of the included articles were reviewed for additional relevant studies.

Data extraction

To ensure accuracy, all reviewers extracted and summarized key information from the included articles so that at least two individuals extracted and summarized the data from each article. The following information was extracted by the authors: author name, date of publication, region of study, type of study, type of arthroplasty, inclusion and exclusion criteria, age, sex, body mass index (BMI), dietary information, the number of participants in each group, the type of protein, amino acid, or placebo given to each group, dosage, route of administration, repetition, overall dose, timing (before, during, or after surgery), period of supplementation intake, exercise or physical therapy details and all outcomes measured. After addressing and resolving any conflicting findings, the final dataset was obtained.

Risk of bias assessment

For quality assessment of randomized controlled trials (RCTs), Cochrane risk of bias tool (ROB), and case-control study, The Newcastle–Ottawa Scale (NOS) was used.

Statistical analysis

We performed a random-effects meta-analysis to assess the effect of PS on quadriceps muscle strength (QMS) and muscle atrophy in patients undergoing arthroplasty by calculating the effect size and corresponding confidence intervals (95%CI). Furthermore, a fixed-effect model was applied for outcomes with low heterogeneity (I2 ≤ 25%). The effect size of our interest in this analysis was Standard Mean Difference or SMD (by Hedges, 1981) using the mean differences from baseline for both supplemented and non-supplemented groups and SD of these mean differences. We have intervention and control groups and mean and SD values of pre and post-operation for each group. So we calculated the mean changes from baseline and SD of the mean changes for each group using the following formula:

$$\text{SD change}=\surd\left(\text{SD}2\text{baseline}+\text{SD}2\text{ final}-\left(2\times \text{r}\times \text{SDbaseline}\times \text{SD} \text{final}\right)\right)$$

SD change represents the SD of the mean changes from baseline, SD baseline represents the SD of pre-op in each group, SD final means the SD post-op in each group, and r represents the correlation between the pre-op and post-op measurements. The first step in calculating the correlation (r in the formula) was to contact the corresponding authors of the included studies to request their data sets or the correlation between the baseline and the final measurements because this correlation value is not generally mentioned in the studies. If the corresponding authors did not share the requested data, we assigned a value of 0.7 to the r in the formula to calculate the SD change. Finally, if there were further missing data in a study, we did not include the study in the meta-analysis. Heterogeneity and inconsistency were assessed using chi-squared (χ2 or Chi2) and I2 statistic. Sensitivity analyses were performed to evaluate the influence of individual studies on the overall effect size for analyses with high heterogeneity. Egger’s regression test was also performed to assess publication bias. P values less than 0.05 were considered statistically significant. All analyses were performed using the R software (version 4.3.2 (2023-10-31)), using the “meta” and “metafor” packages.

Results

Search result

We conducted searches across multiple databases; after removing duplicate entries, we were left with 254 studies for further consideration. Following title/abstract screening and full-text review, 19 articles fulfilled our inclusion criteria [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39] (Fig. 1).

Fig. 1
figure 1

PRISMA flow chart

Study characteristics

These studies were conducted across different countries, with six studies from Japan [28, 30,31,32,33, 37], five from the USA [21, 23, 26, 29, 35], two from Italy [24, 27], two from Sweden [25, 34], two from the UK [36, 38], one from China [39], and one from Iran [22]. In total, 903 patients, 578 of whom were female, were included. 12 articles focused on the arthroplasty of the hip joint [22,23,24,25,26,27,28, 31,32,33,34, 36], while six examined the knee joint [21, 29, 30, 35, 37, 39], and one study focused on both hip and knee joint [38]. 14 articles employed an oral intervention [21, 23, 24, 27,28,29,30,31,32,33, 35, 37,38,39], and five utilized IV intervention [22, 25, 26, 34, 36]. Furthermore, out of the 19 articles, six studies used EAA as the intervention [21, 24, 29, 33, 35, 37], while the remaining studies employed various other types of amino acids. The mean follow-up time was 55.2±84.9 days, ranging from 1 day to 365 days. One article was a case-control study [32], while the remaining were all RCTs (Table 1).

Table 1 Study characteristics

Risk of bias assessment

The domains of selection, which encompass random sequence generation, allocation concealment, and the reporting domain, were more frequently classified as having an unclear risk of bias. Most of the studies were classified as having a low risk of bias, and none of the articles reached a high risk of bias in any of the assessed domains. The case-control study scored eight on the NOS quality assessment [32]. The details of the quality assessment are provided in Fig. 2.

Fig. 2
figure 2

Risk of bias summary and graph

Muscle mass and atrophy

Seven studies have reported on the effects of PS on muscle mass and atrophy, which utilized different measurements to assess these variables and reported their findings using various parameters [21, 28, 30, 31, 35, 37, 39]. EAA, along with age and sex, is an independent factor in preserving muscle atrophy after TKA [37]. EAA consumption significantly affected muscle atrophy in the quadriceps, hamstring, and adductor muscles. Additionally, taking EAA resulted in a significantly higher intramuscular adipose tissue (IMAT) change rate in both legs [21, 35]. Ninomiya et al. found no significant effect of whey protein on IMAT or muscle thickness (MT) [31]. However, Li et al found whey protein and rehabilitation training significantly improved leg circumference as a correlative value to skeletal muscle mass [39]. Furthermore, using HMG/Arg/Gln could reduce rectus femoris muscle atrophy; but the difference compared to the placebo group was insignificant [30]. Ikeda et al reported that BCAA and training significantly affect muscle mass [28] (Table 2). Our meta-analysis showed that PS significantly improved quadriceps femoris muscle mass (SMD: 0.69; 95% CI: 0.44 to 0.95) and hamstring muscle mass (SMD: 1.04; 95% CI: 0.52 to 1.55). However, the effect on upper arm muscle mass was negligible (SMD: 0.12; 95% CI: −0.60 to 0.83). The overall effect size for muscle mass across all muscle groups was 0.70 (95% CI: 0.48 to 0.92), suggesting a beneficial effect of PS (Fig. 3). Subgroup analyses revealed TKA studies had stronger reductions in muscle atrophy (SMD: 0.82) than THA (SMD: 0.43) (Fig. 4). Short-term follow-up (1–6 weeks) showed greater muscle atrophy reduction (SMD: 0.81) than long-term (>6 weeks; SMD: 0.59) (Fig. 5).

Table 2 Muscle mass and atrophy
Fig. 3
figure 3

Forrest plot for muscle atrophy in different muscle groups

Fig. 4
figure 4

Subgroup analysis of muscle atrophy after total knee or total hip arthroplasty

Fig. 5
figure 5

Subgroup analysis of muscle atrophy in short-term (less than 6 weeks) and long-term (more than 6 weeks) follow-up durations

Muscle strength and function

For the assessment of muscle strength, surgeons utilized measures such as quadriceps muscle strength (QMS), hamstring muscle strength (HMS), and HGS. Seven studies have examined the effects of PS on QMS, with the isometric method predominantly used for measurement [21, 28, 30, 31, 35, 37, 39]. Two articles found no correlation between EAA and muscle strength [35, 37]. however, another study observed high QMS improvement rates after using BCAA in both operated and contralateral legs [28]. Dreyer et al the only research measuring QMS at different knee extension angles showed increases at both 45 and 60 degrees for the operated leg and a significant strength increase at 45 degrees in the EAA group [21]. One study found a positive effect of HMG/Arg/Gln on QMS in the operated leg two weeks post-operation, but this effect was not significant by the end of the follow-up period [30]. Ninomiya et al. concluded that whey protein significantly affected QMS on both sides and HMS on the contralateral side [31]. Similarly, Li et al found significantly higher muscle strength with using whey protein [39] (Table 3). Additionally, five studies reported no effect of PS on HGS [28, 31, 33, 35, 37]. Details of these findings are organized in Table 4. A random-effects model was used to analyze the effect of PS on QMS across seven studies. The pooled effect size was 0.9341 (95% CI: −0.2911, 2.1592), indicating a non-significant trend toward improvement in QMS (z = 1.4943, p = 0.1351) with substantial heterogeneity among the studies, with an estimated tau2 = 2.5912 (SE = 1.5789) and I2 = 95.48% with subgroup analyses revealed high QMS heterogeneity in TKA (I2 = 96%) but more consistent effects in THA (I2 = 0%) (Fig. 6). Follow-up duration did not significantly moderate results (p > 0.39) (Fig. 7). Sensitivity analysis was conducted to assess the robustness of the QMS results by systematically removing one study at a time. The results are summarized in Supplementary Table 2.

Table 3 Quadriceps muscle strength
Table 4 Handgrip strength (HGS)
Fig. 6
figure 6

Forrest plot for QMS after total knee or total hip arthroplasty

Fig. 7
figure 7

Subgroup analysis of QMS in short-term (less than 6 weeks) and long-term (more than 6 weeks) follow-up durations

Eight papers have assessed the effects of PS on muscle function [21, 24, 31, 33, 35, 37,38,39]. Various assessments have been utilized with commonly used ones, including the Harris Hip Score (HHS), Timed Up and Go test (TUG-t), the 6-minute walk test, The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and American Knee Score (AKS). Ninomiya et al. found no significant difference in HHS and TUG-t test scores between exercise alone and exercise combined with whey protein [31]. In contrast, Invernizzi et al and Baldassarro et al reported that patients who received EAA performed significantly better in the TUG-t test and HHS [24, 33]. Dreyer et al. observed no statistically significant difference in TUG and 6-minute walk test scores using EAA [35]. However, in another study by Dreyer et al. EAA showed significant improvement in the TUG test but not in the 6-minute walk test [21]. Similarly, Ueyama et al. reported no significant difference in the 6-minute walk test with EAA [37]. Li et al found a significantly higher AKS after using whey protein [39]. Additionally, Khalid et al found a slightly higher median WOMAC score in the PS group compared to the control group [38] (Table 5).

Table 5 Timed Up and Go test (TUG-t)

IV infusion

Five studies infused the amino acids intravenously [22, 25, 26, 34, 36]. Evans et al. found that colloid infusion caused temporary changes in platelet and coagulation parameters without affecting blood loss during hip arthroplasty [36]. Church et al. focused on total hip arthroplasty (THA) and discovered that perioperative amino acid infusion restored muscle net protein balance by augmenting muscle protein synthesis [26]. Widman et al. demonstrated that amino acid infusion promoted thermogenesis during anesthesia, reducing perioperative blood loss [34]. Alipour et al. specifically studied amino acid infusion in hip surgery patients with spinal anesthesia, observing a significant reduction in core body temperature without affecting mean arterial pressure or heart rate [22]. Finally, Blomqvist et al. explored the effects of glutamine and a-ketoglutarate, finding that glutamine infusion prevented glutamine level decreases. In contrast, total free amino acid concentration decreased overall [25]. (A detailed table of changes in each amino acid level is presented in Supplementary-table-1).

Publication bias

Publication bias was assessed using Egger’s regression test for both QMS and muscle atrophy. For QMS, the test results indicated no significant publication bias (z = 1.4241, p = 0.1544) (Fig. 8). Similarly, for muscle atrophy, Egger’s test also showed no significant bias (z = 1.5601, p = 0.1187) (Fig. 9).

Fig. 8
figure 8

Funnel plot Muscle atrophy

Fig. 9
figure 9

Funnel plot for QMS

Discussion

Efficacy of PS for hypertrophy of the elderly, dosage and duration

PS to achieve muscle hypertrophy can be discussed regarding the target population, adequate dosage, sufficient duration of intervention, timing, efficacy of different compounds, and combination with resistance training. In a systematic review and meta-analysis of 17 RCTs, Liao et al. investigated the impact of combined PS and resistance training on lean muscle mass of older people; they concluded that PS improves body composition and function [40]. Conversely, Morton et al.’s study employed meta-regression and subgroup analysis, revealing that PS during resistance training becomes less effective as age increases. Moreover, it does not significantly augment changes in lean body mass among older individuals [41]. The different assumptions might be due to the inclusion of unhealthy older people. Studies suggest that older people benefit from increased dietary protein consumption during catabolic health conditions, e.g., arthroplasty, due to anabolic resistance to muscle protein synthesis [42, 43]. Nunes et al. investigated the impact of increasing daily protein intake on lean body mass in healthy individuals; their meta-analysis suggests that subjects aged ≥65 years consuming 1.2–1.59 g of protein/kg/day and younger individuals (<65 years old) ingesting ≥1.6 g of protein/kg/day significantly increase lean body mass [44]. Other studies have confirmed that a total protein intake of 1.5 to 1.6 g/kg/day has significantly increased muscle strength and volume in elderly individuals with sarcopenia [45,46,47]. Ninomiya et al. only gave 11 g/day of whey protein, which is insufficient stimulation, although baseline protein intake was not measured [31]. On the other hand, Muyskens et al. had 40 g/day of EAA, which seems sufficient, but the supplementation lasted only for 7 days. Protein synthesis is a slow process and requires longer intervention periods to see any significant changes [48]. Studies on sarcopenia indicate that a six-month follow-up has a better impact on improving muscle strength and increasing muscle volume than a three-month follow-up [49].

Quality of the protein

The protein requirements of older adults exhibit heightened reliance on both the quantity and quality of dietary protein. Protein quality is calculated by EAA profile and protein digestibility using established metrics such as the protein digestibility-corrected amino acid score (PDCAAS) or the digestible indispensable amino acid score (DIAAS) [50]. Regarding the different PS options, studies in the field of arthroplasty are focused mainly on EAAs, including leucine [29,30,31,32, 35, 41, 43, 45]. This is plausible because the leucine content in the protein intake of the elderly plays a critical role in maintaining and regaining muscle mass [51]. Ueyama et al. gave 9 g/day of EAAs, providing 0.68 g of leucine [45], and Ikeda et al. supplemented their patients with 3 g/day BCAAs containing 1.2 g of daily leucine [28]. Studies indicate that providing at least 2.5 grams of leucine per meal positively impacts muscle protein synthesis [52, 53]. Leucine content varies across different protein sources, with whey protein containing the highest, approximately 12%, making it one of the best choices due to its affordability relative to isolated amino acids [49, 54, 55]. Ninomya et al. used 11 g/day of a whey protein blend with 2.3 g (21%) of leucine [31].

Exploring other fields of surgery

The importance of hamstring and quadriceps strength on anterior cruciate ligament (ACL) injuries, ACL reconstruction outcomes, and rehabilitation is well established [56], augmenting these efforts with PS shows promising results [57]. Other fields of surgery have conducted similar investigations; for example, in colorectal cancer, Burden et al. used a supplement drink with 24 g/day of protein for at least 10 days before surgery but showed no evidence of reducing the complications [58]. We hypothesize this is because of a very low duration of the supplementation period and insufficient dosage [42,43,44]. Regarding bariatric surgeries, studies have demonstrated that consuming protein leads to a more significant decrease in body fat mass, a more considerable decrease in body weight, and an increase in relative muscle mass in the lower limbs [59,60,61].

Limitations and suggestions

One limitation of this systematic review was the unavailability of all the detailed statistical analyses, so we used a standard value for our correlation analysis. Some of our included studies were underdosed, insufficiently followed, and commonly augmented with exercise or other nutritional supplements, making it hard to conclude the efficacy of PS alone [24, 28, 31, 33, 34, 37]. Another one was the high heterogeneity in QMS meta-analysis, which indicates that the effect of PS may vary significantly depending on factors such as study design, participant characteristics, or type of protein used. We suggest that future research focus on longer PS durations. It’s essential to address the baseline protein intake of the individual and then supplement it to sufficient grams per kg of body weight and evaluate the cost-effectiveness of protein compounds, such as whey protein and EAAs.

Conclusions

This systematic review and meta-analysis suggest that peri-operative protein and amino acid supplementation significantly reduces muscle atrophy in total knee or hip arthroplasty patients. Intravenous delivery also enhances muscle protein synthesis and cuts blood loss. Despite variable strength and function outcomes, supplementation is a key intervention, though further standardized research is warranted.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

OA:

Osteoarthritis

PS:

Protein supplementation

EAA:

Essential amino acids

IMAT:

Intramuscular adipose tissue

BCAA:

Branched-chain amino acid

TKA:

Total knee arthroplasty

THA:

Total hip arthroplasty

TJA:

Total joint arthroplasty

MT:

Muscle thickness

QMS:

Quadriceps muscle strength

HMS:

Hamstring muscle strength

HGS:

Handgrip strength

References

  1. Nguyen US, Zhang Y, Zhu Y, Niu J, Zhang B, Felson DT. Increasing prevalence of knee pain and symptomatic knee osteoarthritis: survey and cohort data. Ann Intern Med. 2011;155(11):725–32. https://doiorg.publicaciones.saludcastillayleon.es/10.7326/0003-4819-155-11-201112060-00004.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Long H, Liu Q, Yin H, Wang K, Diao N, Zhang Y, Lin J, Guo A. Prevalence trends of site-specific osteoarthritis from 1990 to 2019: findings from the global burden of disease study 2019. Arthritis Rheumatol. 2022;74(7):1172–83.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Moxley Scarborough D, Krebs DE, Harris BA. Quadriceps muscle strength and dynamic stability in elderly persons. Gait Posture. 1999;10(1):10–20. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s0966-6362(99)00018-1.

    Article  CAS  PubMed  Google Scholar 

  4. Bertocci GE, Munin MC, Frost KL, Burdett R, Wassinger CA, Fitzgerald SG. Isokinetic performance after total hip replacement. Am J Phys Med Rehabil. 2004;83(1):1–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1097/01.Phm.0000098047.26314.93.

    Article  PubMed  Google Scholar 

  5. Rai J, Gill SS, Kumar BR. The influence of preoperative nutritional status in wound healing after replacement arthroplasty. Orthopedics. 2002;25(4):417–21. https://doiorg.publicaciones.saludcastillayleon.es/10.3928/0147-7447-20020401-17.

    Article  PubMed  Google Scholar 

  6. Fiatarone Singh MA. Exercise, nutrition and managing hip fracture in older persons. Curr Opin Clin Nutr Metab Care. 2014;17(1):12–24. https://doiorg.publicaciones.saludcastillayleon.es/10.1097/mco.0000000000000015.

    Article  CAS  PubMed  Google Scholar 

  7. Stevens-Lapsley JE, Balter JE, Kohrt WM, Eckhoff DG. Quadriceps and hamstrings muscle dysfunction after total knee arthroplasty. Clin Orthop Relat Res®. 2010;468(9):2460–8. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s11999-009-1219-6.

    Article  PubMed  Google Scholar 

  8. Judd DL, Eckhoff DG, Stevens-Lapsley JE. Muscle strength loss in the lower limb after total knee arthroplasty. Am J Phys Med Rehabil. 2012;91:3.

    Article  Google Scholar 

  9. Dreyer HC, Volpi E. Role of protein and amino acids in the pathophysiology and treatment of sarcopenia. J Am Coll Nutr. 2005;24(2):140S-5S. https://doiorg.publicaciones.saludcastillayleon.es/10.1080/07315724.2005.10719455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Roubenoff R. Sarcopenia: effects on body composition and function. J Gerontol A Biol Sci Med Sci. 2003;58(11):M1012–7. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/gerona/58.11.M1012.

    Article  Google Scholar 

  11. Bailey AN, Hocker AD, Vermillion BR, Smolkowski K, Shah SN, Jewett BA, Dreyer HC. Mafbx, murf1, and the stress-activated protein kinases are upregulated in muscle cells during total knee arthroplasty. Am J Physiol Regul Integr Comp Physiol. 2012;303(4):R376-86. https://doiorg.publicaciones.saludcastillayleon.es/10.1152/ajpregu.00146.2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kim HK, Suzuki T, Saito K, Yoshida H, Kobayashi H, Kato H, Katayama M. Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly japanese sarcopenic women: a randomized controlled trial. J Am Geriatr Soc. 2012;60(1):16–23. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/j.1532-5415.2011.03776.x.

    Article  PubMed  Google Scholar 

  13. Liao CD, Lee PH, Hsiao DJ, Huang SW, Tsauo JY, Chen HC, Liou TH. Effects of protein supplementation combined with exercise intervention on frailty indices, body composition, and physical function in frail older adults. Nutrients. 2018;10:12. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/nu10121916.

    Article  CAS  Google Scholar 

  14. Antonio J, Evans C, Ferrando AA, Stout JR, Antonio B, Cintineo HP, Harty P, Arent SM, Candow DG, Forbes SC. Common questions and misconceptions about protein supplementation: what does the scientific evidence really show? J Int Soc Sports Nutr. 2024;21(1):2341903.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nunes EA, Colenso-Semple L, McKellar SR, Yau T, Ali MU, Fitzpatrick-Lewis D, Sherifali D, Gaudichon C, Tomé D, Atherton PJ. Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults. J Cachexia Sarcopenia Muscle. 2022;13(2):795–810.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Ispoglou T, Witard OC, Duckworth LC, Lees MJ. The efficacy of essential amino acid supplementation for augmenting dietary protein intake in older adults: implications for skeletal muscle mass, strength and function. Proc Nutr Soc. 2021;80(2):230–42.

    Article  CAS  PubMed  Google Scholar 

  17. Huecker M, Sarav M, Pearlman M, Laster J. Protein supplementation in sport: source, timing, and intended benefits. Curr Nutr Rep. 2019;8:382–96.

    Article  PubMed  Google Scholar 

  18. de Zwart AH, van der Leeden M, Roorda LD, Visser M, van der Esch M, Lems WF, Dekker J. Dietary protein intake and upper leg muscle strength in subjects with knee osteoarthritis: data from the osteoarthritis initiative. Rheumatol Int. 2019;39(2):277–84. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00296-018-4223-x.

    Article  CAS  PubMed  Google Scholar 

  19. Colker CM, Swain M, Lynch L, Gingerich DA. Effects of a milk-based bioactive micronutrient beverage on pain symptoms and activity of adults with osteoarthritis: a double-blind, placebo-controlled clinical evaluation. Nutrition. 2002;18(5):388–92. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/s0899-9007(01)00800-0.

    Article  CAS  PubMed  Google Scholar 

  20. Zenk JL, Helmer TR, Kuskowski MA. The effects of milk protein concentrate on the symptoms of osteoarthritis in adults: an exploratory, randomized, double-blind, placebo-controlled trial. Curr Ther Res. 2002;63(7):430–42. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/S0011-393X(02)80049-2.

    Article  CAS  Google Scholar 

  21. Dreyer HC, Strycker LA, Senesac HA, Hocker AD, Smolkowski K, Shah SN, Jewett BA. Essential amino acid supplementation in patients following total knee arthroplasty. J Clin Invest. 2013;123(11):4654–66. https://doiorg.publicaciones.saludcastillayleon.es/10.1172/jci70160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Alipour M, TaghaviGillani M, Bameshki A, Razavi M, Mashhadi L, Amiriani M, Peivandi Yazdi A. Evaluation of amino acid infusion preventive effect on hypothermia during spinal anesthesia for hip arthroplasty. Arch Bone Jt Surg. 2022;10(7):627–32. https://doiorg.publicaciones.saludcastillayleon.es/10.22038/abjs.2022.54665.2724.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Askanazi J, Furst P, Michelsen CB, Elwyn DH, Vinnars E, Gump FE, Stinchfield FE, Kinney JM. Muscle and plasma amino acids after injury: hypocaloric glucose vs. amino acid infusion. Ann Surg. 1980;191(4):465–72. https://doiorg.publicaciones.saludcastillayleon.es/10.1097/00000658-198004000-00013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Baldissarro E, Aquilani R, Boschi F, Baiardi P, Iadarola P, Fumagalli M, Pasini E, Verri M, Dossena M, Gambino A, Cammisuli S, Viglio S. The hip functional retrieval after elective surgery may be enhanced by supplemented essential amino acids. Biomed Res Int. 2016;2016:9318329. https://doiorg.publicaciones.saludcastillayleon.es/10.1155/2016/9318329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Blomqvist BI, Hammarqvist F, von der Decken A, Wernerman J. Glutamine and alpha-ketoglutarate prevent the decrease in muscle free glutamine concentration and influence protein synthesis after total hip replacement. Metabolism. 1995;44(9):1215–22. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/0026-0495(95)90019-5.

    Article  CAS  PubMed  Google Scholar 

  26. Church DD, Schutzler SE, Wolfe RR, Ferrando AA. Perioperative amino acid infusion reestablishes muscle net balance during total hip arthroplasty. Physiol Rep. 2021;9(18):e15055. https://doiorg.publicaciones.saludcastillayleon.es/10.14814/phy2.15055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. de Sire A, Baricich A, Renò F, Cisari C, Fusco N, Invernizzi M. Myostatin as a potential biomarker to monitor sarcopenia in hip fracture patients undergoing a multidisciplinary rehabilitation and nutritional treatment: a preliminary study. Aging Clin Exp Res. 2020;32(5):959–62. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s40520-019-01436-8.

    Article  PubMed  Google Scholar 

  28. Ikeda T, Matsunaga Y, Kanbara M, Kamono A, Masuda T, Watanabe M, Nakanishi R, Jinno T. Effect of exercise therapy combined with branched-chain amino acid supplementation on muscle strength in elderly women after total hip arthroplasty: a randomized controlled trial. Asia Pac J Clin Nutr. 2019;28(4):720–6. https://doiorg.publicaciones.saludcastillayleon.es/10.6133/apjcn.201912_28(4).0007.

    Article  CAS  PubMed  Google Scholar 

  29. Muyskens JB, Foote DM, Bigot NJ, Strycker LA, Smolkowski K, Kirkpatrick TK, Lantz BA, Shah SN, Mohler CG, Jewett BA, Owen EC, Dreyer HC. Cellular and morphological changes with eaa supplementation before and after total knee arthroplasty. J Appl Physiol (1985). 2019;127(2):531–45. https://doiorg.publicaciones.saludcastillayleon.es/10.1152/japplphysiol.00869.2018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nishizaki K, Ikegami H, Tanaka Y, Imai R, Matsumura H. Effects of supplementation with a combination of β-hydroxy-β-methyl butyrate, l-arginine, and l-glutamine on postoperative recovery of quadriceps muscle strength after total knee arthroplasty. Asia Pac J Clin Nutr. 2015;24(3):412–20. https://doiorg.publicaciones.saludcastillayleon.es/10.6133/apjcn.2015.24.3.01.

    Article  CAS  PubMed  Google Scholar 

  31. Ninomiya K, Takahira N, Ikeda T, Suzuki K, Sato R, Mihara M. Effects of perioperative exercise therapy combined with nutritional supplementation on functional recovery after fast-track total hip arthroplasty. J Orthop Sci. 2023;28(6):1291–7. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.jos.2022.09.012.

    Article  PubMed  Google Scholar 

  32. Ikeda T, Sato R, Ninomiya K, Suzuki K, Hirakawa K, Jinno T. Nutritional factors related to muscle weakness 1 year after total hip arthroplasty: a case-control study. Ann Nutr Metab. 2022;78(2):73–9. https://doiorg.publicaciones.saludcastillayleon.es/10.1159/000520551.

    Article  CAS  PubMed  Google Scholar 

  33. Invernizzi M, de Sire A, D’Andrea F, Carrera D, Renò F, Migliaccio S, Iolascon G, Cisari C. Effects of essential amino acid supplementation and rehabilitation on functioning in hip fracture patients: a pilot randomized controlled trial. Aging Clin Exp Res. 2019;31(10):1517–24. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s40520-018-1090-y.

    Article  PubMed  Google Scholar 

  34. Widman J, Hammarqvist F, Selldén E. Amino acid infusion induces thermogenesis and reduces blood loss during hip arthroplasty under spinal anesthesia. Anesth Analg. 2002;95(6):1757–62. https://doiorg.publicaciones.saludcastillayleon.es/10.1097/00000539-200212000-00053. Table of contents.

    Article  CAS  PubMed  Google Scholar 

  35. Dreyer HC, Owen EC, Strycker LA, Smolkowski K, Muyskens JB, Kirkpatrick TK, Christie AD, Kuehl KS, Lantz BA, Shah SN, Mohler CG, Jewett BA. Essential amino acid supplementation mitigates muscle atrophy after total knee arthroplasty: a randomized, double-blind, placebo-controlled trial. JB JS Open Access. 2018;3(2):e0006. https://doiorg.publicaciones.saludcastillayleon.es/10.2106/jbjs.Oa.18.00006.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Evans PA, Heptinstall S, Crowhurst EC, Davies T, Glenn JR, Madira W, Davidson SJ, Burman JF, Hoskinson J, Stray CM. Prospective double-blind randomized study of the effects of four intravenous fluids on platelet function and hemostasis in elective hip surgery. J Thromb Haemost. 2003;1(10):2140–8. https://doiorg.publicaciones.saludcastillayleon.es/10.1046/j.1538-7836.2003.00411.x.

    Article  CAS  PubMed  Google Scholar 

  37. Ueyama H, Kanemoto N, Minoda Y, Taniguchi Y, Nakamura H. Perioperative essential amino acid supplementation facilitates quadriceps muscle strength and volume recovery after tka: a double-blinded randomized controlled trial. J Bone Joint Surg Am. 2023;105(5):345–53. https://doiorg.publicaciones.saludcastillayleon.es/10.2106/jbjs.22.00675.

    Article  PubMed  Google Scholar 

  38. Khalid T, Ben-Shlomo Y, Bertram W, Culliford L, Henderson EJ, Jepson M, Johnson E, Mitchell A, Palmer S, Evans JT, Whitehouse MR, Wylde V. Prehabilitation for frail patients undergoing hip and knee replacement in the UK: joint prep feasibility study for a randomised controlled trial. BMJ Open. 2024;14(9):e084678. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/bmjopen-2024-084678.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Li M, Shi Q, Che X, Du X, Wang D, Song Y. Study of whey protein on muscle mass and functional rehabilitation in postoperative total knee arthroplasty patients. J Back Musculoskelet Rehabil. 2024;37(5):1381–90. https://doiorg.publicaciones.saludcastillayleon.es/10.3233/bmr-240013.

    Article  PubMed  Google Scholar 

  40. Liao CD, Tsauo JY, Wu YT, Cheng CP, Chen HC, Huang YC, Chen HC, Liou TH. Effects of protein supplementation combined with resistance exercise on body composition and physical function in older adults: a systematic review and meta-analysis12. Am J Clin Nutr. 2017;106(4):1078–91. https://doiorg.publicaciones.saludcastillayleon.es/10.3945/ajcn.116.143594.

    Article  CAS  PubMed  Google Scholar 

  41. Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018;52(6):376. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/bjsports-2017-097608.

    Article  PubMed  Google Scholar 

  42. Phillips SM, Paddon-Jones D, Layman DK. Optimizing adult protein intake during catabolic health conditions. Adv Nutr. 2020;11(4):S1058-s69. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/advances/nmaa047.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Breen L, Phillips SM. Skeletal muscle protein metabolism in the elderly: interventions to counteract the ‘anabolic resistance’ of ageing. Nutr Metab (Lond). 2011;8:68. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/1743-7075-8-68.

    Article  CAS  PubMed  Google Scholar 

  44. Nunes EA, Colenso-Semple L, McKellar SR, Yau T, Ali MU, Fitzpatrick-Lewis D, Sherifali D, Gaudichon C, Tomé D, Atherton PJ, Robles MC, Naranjo-Modad S, Braun M, Landi F, Phillips SM. Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults. J Cachexia Sarcopenia Muscle. 2022;13(2):795–810. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jcsm.12922.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Deutz NE, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, Cederholm T, Cruz-Jentoft A, Krznariç Z, Nair KS, Singer P, Teta D, Tipton K, Calder PC. Protein intake and exercise for optimal muscle function with aging: recommendations from the espen expert group. Clin Nutr. 2014;33(6):929–36. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.clnu.2014.04.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mitchell CJ, Milan AM, Mitchell SM, Zeng N, Ramzan F, Sharma P, Knowles SO, Roy NC, Sjödin A, Wagner KH, Cameron-Smith D. The effects of dietary protein intake on appendicular lean mass and muscle function in elderly men: a 10-wk randomized controlled trial. Am J Clin Nutr. 2017;106(6):1375–83. https://doiorg.publicaciones.saludcastillayleon.es/10.3945/ajcn.117.160325.

    Article  CAS  PubMed  Google Scholar 

  47. Tagawa R, Watanabe D, Ito K, Otsuyama T, Nakayama K, Sanbongi C, Miyachi M. Synergistic effect of increased total protein intake and strength training on muscle strength: A dose-response meta-analysis of randomized controlled trials. Sports Med Open. 2022;8(1):110. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40798-022-00508-w.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Sartori R, Romanello V, Sandri M. Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun. 2021;12(1):330. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41467-020-20123-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Liao CD, Huang SW, Chen HC, Huang MH, Liou TH, Lin CL. Comparative efficacy of different protein supplements on muscle mass, strength, and physical indices of sarcopenia among community-dwelling, hospitalized or institutionalized older adults undergoing resistance training: a network meta-analysis of randomized controlled trials. Nutrients. 2024;16:7. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/nu16070941.

    Article  CAS  Google Scholar 

  50. Dietary protein quality evaluation in human nutrition. Report of an faq expert consultation. FAO Food Nutr Pap. 2013;92:1–66.

    Google Scholar 

  51. Devries MC, McGlory C, Bolster DR, Kamil A, Rahn M, Harkness L, Baker SK, Phillips SM. Protein leucine content is a determinant of shorter- and longer-term muscle protein synthetic responses at rest and following resistance exercise in healthy older women: a randomized, controlled trial. Am J Clin Nutr. 2018;107(2):217–26. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/ajcn/nqx028.

    Article  PubMed  Google Scholar 

  52. Devries MC, McGlory C, Bolster DR, Kamil A, Rahn M, Harkness L, Baker SK, Phillips SM. Leucine, not total protein, content of a supplement is the primary determinant of muscle protein anabolic responses in healthy older women. J Nutr. 2018;148(7):1088–95. https://doiorg.publicaciones.saludcastillayleon.es/10.1093/jn/nxy091.

    Article  PubMed  Google Scholar 

  53. Murphy CH, Saddler NI, Devries MC, McGlory C, Baker SK, Phillips SM. Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study. Am J Clin Nutr. 2016;104(6):1594–606. https://doiorg.publicaciones.saludcastillayleon.es/10.3945/ajcn.116.136424.

    Article  CAS  PubMed  Google Scholar 

  54. Gorissen SHM, Crombag JJR, Senden JMG, Waterval WAH, Bierau J, Verdijk LB, van Loon LJC. Protein content and amino acid composition of commercially available plant-based protein isolates. Amino Acids. 2018;50(12):1685–95. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s00726-018-2640-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cuyul-Vásquez I, Pezo-Navarrete J, Vargas-Arriagada C, Ortega-Díaz C, Sepúlveda-Loyola W, Hirabara SM, Marzuca-Nassr GN. Effectiveness of whey protein supplementation during resistance exercise training on skeletal muscle mass and strength in older people with sarcopenia: a systematic review and meta-analysis. Nutrients. 2023;15:15. https://doiorg.publicaciones.saludcastillayleon.es/10.3390/nu15153424.

    Article  CAS  Google Scholar 

  56. Eitzen I, Holm I, Risberg MA. Preoperative quadriceps strength is a significant predictor of knee function two years after anterior cruciate ligament reconstruction. Br J Sports Med. 2009;43(5):371. https://doiorg.publicaciones.saludcastillayleon.es/10.1136/bjsm.2008.057059.

    Article  CAS  PubMed  Google Scholar 

  57. Holm L, Esmarck B, Mizuno M, Hansen H, Suetta C, Hölmich P, Krogsgaard M, Kjaer M. The effect of protein and carbohydrate supplementation on strength training outcome of rehabilitation in acl patients. J Orthop Res. 2006;24(11):2114–23. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/jor.20147.

    Article  CAS  PubMed  Google Scholar 

  58. Burden ST, Hill J, Shaffer JL, Campbell M, Todd C. An unblinded randomised controlled trial of preoperative oral supplements in colorectal cancer patients. J Hum Nutr Diet. 2011;2(5):441–8. https://doiorg.publicaciones.saludcastillayleon.es/10.1111/j.1365-277X.2011.01188.x.

    Article  Google Scholar 

  59. Oppert JM, Bellicha A, Roda C, Bouillot JL, Torcivia A, Clement K, Poitou C, Ciangura C. Resistance training and protein supplementation increase strength after bariatric surgery: a randomized controlled trial. Obesity (Silver Spring). 2018;26(11):1709–20. https://doiorg.publicaciones.saludcastillayleon.es/10.1002/oby.22317.

    Article  CAS  PubMed  Google Scholar 

  60. Schollenberger AE, Karschin J, Meile T, Küper MA, Königsrainer A, Bischoff SC. Impact of protein supplementation after bariatric surgery: a randomized controlled double-blind pilot study. Nutrition. 2016;32(2):186–92. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.nut.2015.08.005.

    Article  CAS  PubMed  Google Scholar 

  61. Lopes Gomes D, Moehlecke M, Lopes da Silva FB, Dutra ES, D’Agord Schaan B, Baiocchi de Carvalho KM. Whey protein supplementation enhances body fat and weight loss in women long after bariatric surgery: a randomized controlled trial. Obes Surg. 2017;27(2):424–31. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s11695-016-2308-8.

    Article  PubMed  Google Scholar 

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All authors contributed substantially to this study. Also, all authors read and approved the final manuscript. Amir Mehrvar and Mohammad Noroozi conceptualized and supervised the study and reviewed and revised the final draft. Yashar Khani developed the methodology, administered the steps, reviewed and edited the final manuscript, and validated the data extraction sheet. Study selection, risk of bias assessment, data extraction, and writing the original draft were done by Ali Salmani, Elias Sadooghi Rad, Shaghayegh Karami, Mohammad Elahi, Alireza Bahrami Samani, and Iman Elahi Vahed. Iman Elahi Vahed conducted the meta-analysis.

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Khani, Y., Salmani, A., Elahi, M. et al. Peri-operative protein or amino acid supplementation for total joint arthroplasty: a systematic review and meta-analysis. J Orthop Surg Res 20, 439 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13018-025-05847-4

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