Nutritional Supplements for Musculoskeletal Health¶
Evidence on dietary supplements for joint, muscle and bone health — protein and amino acids, creatine, collagen peptides, glucosamine and chondroitin, and omega-3 — including perioperative recovery and osteoarthritis.
Overview¶
Nutritional supplementation represents a low-risk intervention strategy with demonstrated benefits across diverse orthopaedic populations, ranging from osteoarthritis management to peri-operative recovery. Glucosamine and chondroitin sulfate exhibit an excellent safety profile and may serve as an initial treatment modality for many osteoarthritis patients [1]. Specifically, glucosamine sulfate reduces pain, improves function, and may regulate joint damage in knee osteoarthritis [6]. Furthermore, non-steroidal anti-inflammatory drugs and glucosamine sulfate may have a synergic action for the treatment of knee osteoarthritis [6].
In the context of surgical recovery, peri-operative intravenous protein or amino acid supplementation offers benefits for total joint arthroplasty, although effects on muscle strength and function are mixed [2]. Integrating targeted nutrition into prehabilitation pathways for total joint arthroplasty may help reduce complications and support faster functional gains [9]. Nutritional supplementation markedly reduces hospital costs by reducing rates of ICU admissions, hospital-associated complications, and hospital-acquired infections in orthopaedic surgery [5].
Adjuvant oral supplementation containing collagen, hyaluronic acid, chondroitin sulfate, and plasma proteins may increase the efficacy of physical therapy after anterior cruciate ligament reconstruction by shortening the time needed to return to pre-injury activity [3]. This same regimen may reduce analgesic consumption after anterior cruciate ligament reconstruction [3]. For geriatric patients with sarcopenia, especially those unable to exercise, specific nutritional supplementation with vitamin D and leucine-enriched whey protein may provide benefit [4]. Conditionally essential amino acid supplementation has a protective effect against common complications and early skeletal muscle wasting after operative fixation of extremity and pelvic fractures [7].
For older people undergoing hip fracture aftercare, oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality [8]. However, substantial barriers to nutritional optimization in spine surgery include inconsistent protocols and patient nonadherence [11]. Standardization of multidisciplinary nutritional protocols is needed for spine surgery due to these barriers [11].
Background & Causes¶
Glucosamine and Chondroitin Sulfate: These agents possess an excellent safety profile [1] and may serve as an initial treatment modality for many osteoarthritis (OA) patients [1]. Evidence supports their efficacy in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis [6]. Glucosamine sulfate specifically shows potential to relieve pain and improve function with low side effects [10]. However, substantial barriers to definitive endorsement remain due to unanswered questions regarding long-term effects and dosage [10], and the current lack of substantial evidence prevents a ringing endorsement of these agents [10].
Omega-3 Fatty Acids: Supplementation of n-3 polyunsaturated fatty acids (PUFAs) is effective to relieve pain and improve joint function in patients with osteoarthritis [12]. Omega-3 fatty acids protect cartilage from acute injuries by reducing the mechanical sensitivity of chondrocytes [17]. EPA supplementation could offer a promising strategy for preventing post-traumatic osteoarthritis (PTOA) progression following acute cartilage injuries [17].
Collagen Peptides: Collagen peptide supplementation has analgesic efficacy in knee osteoarthritis [19]. The risk of adverse events did not differ significantly between the collagen peptide group and the placebo group [19].
Protein and Amino Acid Supplementation: Intravenous protein or amino acid supplementation offers benefits in total joint arthroplasty, although effects on muscle strength and function are mixed [2]. Protein supplementation appears to have beneficial effects on mitigating muscle atrophy in the postoperative period following ACL reconstruction, total hip arthroplasty, total knee arthroplasty, and surgical treatment of hip fracture [15]. It is a low-cost intervention that is easy to incorporate into perioperative management and has beneficial effects on muscle strength, which could potentially reduce the risk of longer-term complications such as falls and periprosthetic fracture after total knee arthroplasty [18]. Conditionally essential amino acid (CEAA) supplementation has a protective effect against common complications and early skeletal muscle wasting after operative fixation of extremity and pelvic fractures [7].
Adjuvant and Geriatric Supplementation: Adjuvant oral supplementation containing collagen, hyaluronic acid, chondroitin sulfate, and plasma proteins may increase the efficacy of physical therapy by shortening the time needed to return to pre-injury activity and reducing analgesic consumption after anterior cruciate ligament reconstruction [3]. Specific nutritional supplementation alone may benefit geriatric patients, especially those unable to exercise [4]. Oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality in hip fracture aftercare for older people [8].
Clinical and Economic Impact: Integrating targeted nutrition into prehabilitation pathways may help reduce complications and support faster functional gains in total joint arthroplasty [9]. Nutritional supplementation markedly reduces hospital costs by reducing rates of ICU admissions, hospital-associated complications, and hospital-acquired infections [5]. Substantial barriers to nutritional optimization in spine surgery include inconsistent protocols and patient nonadherence, highlighting the need for multifactorial assessment and standardization of multidisciplinary nutritional protocols [11].
Symptoms & Presentation¶
Glucosamine and Chondroitin Sulfate: These agents possess an excellent safety profile [1] and may serve as an initial treatment modality for many osteoarthritis (OA) patients [1]. Evidence supports their efficacy in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis, particularly when compared with non-steroidal anti-inflammatory drugs [6]. Oral chondroitin is more effective than placebo on relieving pain and improving physical function in osteoarthritis [16], while glucosamine showed an effect on stiffness outcomes in osteoarthritis [16]. Glucosamine sulfate specifically has potential to relieve pain and improve function with low side effects [10].
Limitations and Endorsement: Unanswered questions regarding long-term effects and dosage of glucosamine sulfate preclude a definitive endorsement [10]. Lack of substantial evidence currently prevents a ringing endorsement of glucosamine and chondroitin agents [10]. However, glucosamine and chondroitin sulfate may be considered reasonable treatment options as part of a multimodal approach for symptomatic primary osteoarthritis if the cost is not prohibitive [13].
n-3 Polyunsaturated Fatty Acids (PUFAs): Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with osteoarthritis [12].
Collagen Peptides: Collagen peptide supplementation has analgesic efficacy in knee osteoarthritis [19]. The risk of adverse events did not differ significantly between the collagen peptide group and the placebo group in knee osteoarthritis [19]. An eight-week collagen-based supplement had a positive effect on pain and quality of life levels in patients with meniscopathy [14]. An eight-week collagen-based supplement had a positive effect on some functional test results in patients with meniscopathy [14].
Management¶
Glucosamine and Chondroitin: These agents possess an excellent safety profile and may serve as an initial treatment modality for many osteoarthritis (OA) patients [1]. Glucosamine sulfate has potential to relieve pain and improve function with low side effects, though unanswered questions regarding long-term effects and dosage preclude a definitive endorsement [10]. There is a lack of substantial evidence currently preventing a ringing endorsement of glucosamine and chondroitin agents [10]. Evidence supports the efficacy of glucosamine sulfate in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis [6]. Glucosamine sulfate may have a possible synergic action with non-steroidal anti-inflammatory drugs for the treatment of knee osteoarthritis [6]. Oral chondroitin is more effective than placebo on relieving pain and improving physical function in osteoarthritis [16]. Glucosamine showed an effect on stiffness outcomes in osteoarthritis [16]. If cost is not prohibitive, glucosamine and chondroitin products may be considered reasonable treatment options as part of a multimodal approach for symptomatic primary osteoarthritis [13].
Omega-3 Polyunsaturated Fatty Acids (PUFAs): Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with osteoarthritis [12]. EPA supplementation could offer a promising strategy for preventing post-traumatic osteoarthritis (PTOA) progression following acute cartilage injuries by protecting cartilage from acute injury [17].
Collagen and Adjuvant Supplements: Adjuvant oral supplementation containing collagen, hyaluronic acid, chondroitin sulfate, and plasma proteins may increase the efficacy of physical therapy by shortening the time needed to return to pre-injury activity and reducing analgesic consumption after anterior cruciate ligament (ACL) reconstruction [3]. Collagen-based supplementation (type I and III collagen peptide and type II hydrolyzed collagen) had a positive effect on pain, quality of life levels, and some functional test results in patients with meniscopathy [14].
Protein and Amino Acid Supplementation: Intravenous protein or amino acid supplementation offers benefits in total joint arthroplasty, although effects on muscle strength and function are mixed [2]. Protein supplementation appears to have beneficial effects on mitigating muscle atrophy in the postoperative period following ACL reconstruction, total hip arthroplasty (THA), total knee arthroplasty (TKA), and surgical treatment of hip fracture [15]. Protein supplementation is a low-cost intervention that is easy to incorporate into perioperative management, with beneficial effects on muscle strength that could potentially reduce the risk of longer-term complications such as falls and periprosthetic fracture after total knee arthroplasty [18]. Conditionally essential amino acid (CEAA) supplementation has a protective effect against common complications and early skeletal muscle wasting after operative fixation of extremity and pelvic fractures [7]. Specific nutritional supplementation with vitamin D and leucine-enriched whey protein shows proof-of-principle that it might benefit geriatric patients, especially those unable to exercise [4].
General Nutritional Support: Nutritional supplementation markedly reduces hospital costs by reducing rates of ICU admissions, hospital-associated complications, and hospital-acquired infections in orthopaedic surgery [5]. Oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality in hip fracture aftercare for older people [8]. Integrating targeted nutrition into prehabilitation pathways may help reduce complications and support faster functional gains in total joint arthroplasty [9].
Creatine: Patients do not benefit from creatine supplementation during the first 12 weeks of rehabilitation after ACL reconstruction [21].
Key Considerations¶
Glucosamine and Chondroitin Sulfate: These agents possess an excellent safety profile and may serve as an initial treatment modality for many osteoarthritis patients [1]. They exhibit potential synergic action with non-steroidal anti-inflammatory drugs in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis [6]. For symptomatic primary osteoarthritis of the hand, these supplements are reasonable treatment options as part of a multimodal approach if cost is not prohibitive [13]. However, the lack of substantial evidence currently prevents a definitive endorsement for general osteoarthritis management due to unanswered questions regarding long-term effects and dosage [10]. A long-term randomized clinical trial is designed to examine the symptom-modifying and disease-modifying effectiveness of glucosamine sulfate in hip osteoarthritis [20].
Peri-operative and Prehabilitation Nutrition: Integrating targeted nutrition into prehabilitation pathways may help reduce complications and support faster functional gains in total joint arthroplasty [9]. Peri-operative intravenous protein or amino acid supplementation offers benefits for total joint arthroplasty, although effects on muscle strength and function are mixed [2]. Adjuvant oral supplementation containing collagen, hyaluronic acid, chondroitin sulfate, and plasma proteins may increase the efficacy of physical therapy after anterior cruciate ligament reconstruction by shortening the time to return to pre-injury activity and reducing analgesic consumption [3].
Geriatric and Fracture Care: Specific nutritional supplementation with vitamin D and leucine-enriched whey protein may benefit geriatric patients, particularly those unable to exercise [4]. Oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality in hip fracture aftercare for older people [8]. Comprehensive balanced nutrition supplementation resulted in lower complication rates and mortality at 120 days postoperatively for hip fracture patients [23]. Conditionally essential amino acid supplementation has a protective effect against common complications and early skeletal muscle wasting after operative fixation of extremity and pelvic fractures [7].
Spine Surgery and General Impact: Substantial barriers to nutritional optimization in spine surgery include inconsistent protocols and patient nonadherence, necessitating standardization of multidisciplinary nutritional protocols [11]. Nutritional supplementation markedly reduces hospital costs by reducing rates of ICU admissions, hospital-associated complications, and hospital-acquired infections [5].
Comparative Efficacy: Hydrolyzed collagen demonstrated a more sustained therapeutic effect in terms of pain relief and functional improvement compared to hyaluronic acid and platelet-rich plasma over a one-year period in symptomatic knee osteoarthritis [24].
Key Evidence¶
- [L2] The excellent safety profile of these supplements should be discussed with patients, and they may serve a role as an initial treatment modality for many OA patients. (10.1016/j.arthro.2008.07.020)
- [L1] While effects on muscle strength and function are mixed, intravenous supplementation offers benefits. (10.1186/s13018-025-05847-4)
- [L1] Adjuvant oral supplementation may increase the efficacy of physical therapy by shortening the time needed to return to pre-injury activity and the analgesic consumption. (10.1177/2325967118s00040)
- [L1] This study shows proof-of-principle that specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise. (10.1016/j.jamda.2015.05.021)
- [L4] Nutritional supplementation has been shown to markedly reduce hospital costs by reducing rates of ICU admissions, hospital-associated complications, and hospital-acquired infections. (10.5435/jaaos-d-23-00300)
- [L4] The evidence supports efficacy in reducing pain, improving function, and possibly regulating joint damage. (10.1186/s12891-022-06046-6)
- [L1] CEAA supplementation has a protective effect against common complications and early skeletal muscle wasting after operative fixation of extremity and pelvic fractures. (10.2106/jbjs.21.01014)
- [L1] However, oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality. (10.1097/corr.0000000000000658)
- [L4] Integrating targeted nutrition into prehabilitation pathways may help reduce complications and support faster functional gains. (10.1016/j.arth.2026.03.088)
- [L5] The authors conclude that while glucosamine sulfate has potential to relieve pain and improve function with low side effects, unanswered questions regarding long-term effects and dosage preclude a definitive endorsement, and the lack of substantial evidence currently prevents a ringing endorsement of these agents. (10.5435/00124635-200109000-00009)
- [L4] Despite these benefits, substantial barriers like inconsistent protocols and patient nonadherence remain, highlighting the need for multifactorial assessment and standardization of multidisciplinary nutritional protocols. (10.5435/jaaos-d-25-00757)
- [L1] Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with OA. (10.1186/s13018-023-03855-w)
- [L4] If the cost is not prohibitive, these products may be considered reasonable treatment options as part of a multimodal approach for symptomatic primary osteoarthritis. (10.1016/j.jhsa.2013.05.017)
- [L1] The results of the study showed that the eight-week collagen-based supplement had a positive effect on pain and quality of life levels and some functional test results in patients with meniscopathy. (10.1186/s12891-024-08244-w)
- [L1] Protein supplementation appears to have beneficial effects on mitigating muscle atrophy in the postoperative period following ACLR, THA, TKA, and surgical treatment of hip fracture. (10.1177/2325967123s00326)
- [L1] Oral chondroitin is more effective than placebo on relieving pain and improving physical function, while glucosamine showed effect on stiffness outcome. (10.1186/s13018-018-0871-5)
- [L5] The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. (10.1186/s13018-024-05081-4)
- [L5] Protein supplementation is a low-cost intervention that is easy to incorporate into perioperative management, and the beneficial effects on muscle strength could potentially reduce the risk of longer-term complications, such as falls and periprosthetic fracture. (10.2106/jbjs.22.01357)
- [L1] In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. (10.1186/s13018-023-04182-w)
- [L2] This article presents the design of a long-term randomised clinical trial to examine the symptom-modifying and disease-modifying effectiveness of glucosamine sulphate in patients with hip osteoarthritis. (10.1186/1471-2474-6-20)
- [L1] The results demonstrate that patients do not benefit from creatine supplementation during the first 12 weeks of rehabilitation after ACL reconstruction. (10.1177/0363546503261731)
- [L1] The comprehensive balanced nutrition supplement resulted in lower complication rates and mortality at 120 days postoperatively. (10.1097/01.blo.0000224054.86625.06)
- [L3] In this retrospective study, hydrolyzed collagen demonstrated a more sustained therapeutic effect in terms of pain relief and functional improvement compared to hyaluronic acid and platelet-rich plasma over a one-year period. (10.1186/s12891-025-08811-9)
References¶
[1] A Review of Evidence‐Based Medicine for Glucosamine and Chondroitin Sulfate Use in Knee Osteoarthritis. Arthroscopy. 2008. DOI: 10.1016/j.arthro.2008.07.020
[2] Peri-operative protein or amino acid supplementation for total joint arthroplasty: a systematic review and meta-analysis. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-05847-4
[3] Efficacy and Tolerability of a Dietary Supplement Containing Collagen, Hyaluronic Acid, Chondroitin Sulfate and Plasma Proteins in the Recovery After Anterior Cruciate Ligament Reconstruction. Orthopaedic Journal of Sports Medicine. 2018. DOI: 10.1177/2325967118s00040
[4] Effects of a Vitamin D and Leucine-Enriched Whey Protein Nutritional Supplement on Measures of Sarcopenia in Older Adults, the PROVIDE Study: A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of the American Medical Directors Association. 2015. DOI: 10.1016/j.jamda.2015.05.021
[5] The Role of Amino Acid Supplementation in Orthopaedic Surgery. Journal of the American Academy of Orthopaedic Surgeons. 2023. DOI: 10.5435/jaaos-d-23-00300
[6] Possible synergic action of non-steroidal anti-inflammatory drugs and glucosamine sulfate for the treatment of knee osteoarthritis: a scoping review. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-06046-6
[7] Conditionally Essential Amino Acid Supplementation Reduces Postoperative Complications and Muscle Wasting After Fracture Fixation. Journal of Bone and Joint Surgery. 2022. DOI: 10.2106/jbjs.21.01014
[8] Cochrane in CORR®: Nutritional Supplementation for Hip Fracture Aftercare in Older People. Clinical Orthopaedics & Related Research. 2019. DOI: 10.1097/corr.0000000000000658
[9] Perioperative Nutritional Optimization in Total Joint Arthroplasty: From Screening to Supplementation. The Journal of Arthroplasty. 2026. DOI: 10.1016/j.arth.2026.03.088
[10] Use of Glucosamine and Chondroitin Sulfate in the Management of Osteoarthritis. Journal of the American Academy of Orthopaedic Surgeons. 2001. DOI: 10.5435/00124635-200109000-00009
[11] Nutritional Optimization in Spine Surgery: A Review of Its Implications for Postoperative Recovery and Outcomes. Journal of the American Academy of Orthopaedic Surgeons. 2026. DOI: 10.5435/jaaos-d-25-00757
[12] Effect of omega-3 polyunsaturated fatty acids supplementation for patients with osteoarthritis: a meta-analysis. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-03855-w
[13] Glucosamine and Chondroitin Sulfate Treatment of Hand Osteoarthritis. The Journal of Hand Surgery. 2013. DOI: 10.1016/j.jhsa.2013.05.017
[14] The effect of supplementation with type I and type III collagen peptide and type II hydrolyzed collagen on pain, quality of life and physical function in patients with meniscopathy: a randomized, double-blind, placebo-controlled study. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-024-08244-w
[15] Poster 363: Post-Operative Protein Supplementation following Orthopaedic Surgery: A Systematic Review. Orthopaedic Journal of Sports Medicine. 2023. DOI: 10.1177/2325967123s00326
[16] Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials. Journal of Orthopaedic Surgery and Research. 2018. DOI: 10.1186/s13018-018-0871-5
[17] Omega-3 fatty acids protect cartilage from acute injurie by reducing the mechanical sensitivity of chondrocytes. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-05081-4
[18] Nutritional Optimization with Amino Acid Supplementation Aids Recovery After Total Knee Arthroplasty. Journal of Bone and Joint Surgery. 2023. DOI: 10.2106/jbjs.22.01357
[19] Analgesic efficacy of collagen peptide in knee osteoarthritis: a meta-analysis of randomized controlled trials. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-04182-w
[20] The effect of glucosamine sulphate on osteoarthritis: design of a long-term randomised clinical trial [ISRCTN54513166]. BMC Musculoskeletal Disorders. 2005. DOI: 10.1186/1471-2474-6-20
[21] The Effect of Creatine Supplementation on Strength Recovery after Anterior Cruciate Ligament (ACL) Reconstruction. The American Journal of Sports Medicine. 2004. DOI: 10.1177/0363546503261731
[23] Nutritional Supplementation Decreases Hip Fracture-related Complications. Clinical Orthopaedics and Related Research. 2006. DOI: 10.1097/01.blo.0000224054.86625.06
[24] Efficacy of hydrolyzed collagen injections compared to platelet-rich plasma and hyaluronic acid in the treatment of patients with symptomatic knee osteoarthritis: a retrospective clinical study. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08811-9