Nutritional Supplements for Musculoskeletal Health Info Evidence

This is the clinical evidence summary written for health professionals. It is technical, and it lists the research this page was built from. You do not need to read it to understand your treatment or to make a decision about it.

Overview

• Peptide supplements should not currently be recommended as a replacement or adjunct for existing orthopaedic standard of care due to the lack of robust efficacy and safety data [1].
• Specific nutritional supplementation alone might benefit geriatric patients, especially those who are unable to exercise [2].
• Intravenous perioperative protein or amino acid supplementation offers benefits for total joint arthroplasty, while effects on muscle strength and function are mixed [3].
• Glucosamine and chondroitin sulfate have an excellent safety profile and may serve a role as an initial treatment modality for many osteoarthritis patients [4].
• 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 [5].
• Supplementation of n-3 polyunsaturated fatty acids is effective to relieve pain and improve joint function in patients with osteoarthritis [6].
• The combination of non-steroidal anti-inflammatory drugs and glucosamine sulfate supports efficacy in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis [7].
• Supplementation with omega-3 polyunsaturated fatty acids for 3-4 months reduces patient-reported joint pain intensity, minutes of morning stiffness, number of painful and/or tender joints, and NSAID consumption [8].
• 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 [9].
• Glucosamine sulfate has the potential to relieve pain and improve function with low side effects, but unanswered questions regarding long-term effects and dosage preclude a definitive endorsement [10].
• Nutrition consultation and perioperative supplementation with amino acids and micronutrients are readily available interventions that orthopaedic surgeons can select for malnourished patients [11].
• The appropriate use of some dietary supplements can benefit the athlete, while others may harm the athlete’s health, performance, and/or livelihood and reputation if an antidoping rule violation results [12].
• Nutritional supplementation has been shown to markedly reduce hospital costs by reducing rates of ICU admissions, hospital-associated complications, and hospital-acquired infections [13].
• Glucosamine and chondroitin sulfate may be considered reasonable treatment options as part of a multimodal approach for symptomatic primary hand osteoarthritis if the cost is not prohibitive [14].
• Recommendations for data capture relating to female athlete population characteristics, injuries, illnesses, and other health consequences will improve the quality of epidemiological studies to inform better injury and illness prevention strategies [15].
• The use of low-cost commercially available amino acid supplements resulted in fewer overall complications postoperatively and was a low-risk intervention for the patient population [19].
• Substantial barriers such as inconsistent protocols and patient nonadherence remain in nutritional optimization for spine surgery, highlighting the need for multifactorial assessment and standardization of multidisciplinary nutritional protocols [22].
• Perioperative nutritional optimization has been associated with improved outcomes for patients undergoing spine surgery, but additional investigation is needed to determine effective perioperative nutritional protocols [23].

How It Works

Mechanisms of Action

• Glucosamine may exert analgesic properties through the stimulation of hyaluronic acid production in human osteoarthritic synovium [32].
• Omega-3 fatty acids protect cartilage from acute injury by reducing the mechanical sensitivity of chondrocytes [16].

Perioperative and Postoperative Recovery

• Perioperative essential amino acid supplementation prevents rectus femoris muscle atrophy and accelerates early functional recovery after total knee arthroplasty [30].
• 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 [24].
• Protein supplementation is a low-cost intervention that is easy to incorporate into perioperative management, and its beneficial effects on muscle strength could potentially reduce the risk of longer-term complications such as falls and periprosthetic fracture [20].
• Oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality in older people after hip fracture [17].

Osteoarthritis and Joint Pain

• Collagen peptides provide significant pain relief in patients with knee osteoarthritis compared to placebo [27].
• An eight-week collagen-based supplement has a positive effect on pain, quality of life levels, and some functional test results in patients with meniscopathy [25].
• Subacromial injection of hydrolyzed collagen is effective in reducing pain and supporting functional recovery in patients with rotator cuff tendinopathy, with effects observed after the first injection and persisting up to six months [29].
• Glucosamine sulfate has the 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].
• The evidence supports the efficacy of glucosamine sulfate in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis [7].

Muscle Mass and Strength

• Protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute to resistance training-induced gains in fat-free mass [18].

Limitations and Safety

• Patients do not benefit from creatine supplementation during the first 12 weeks of rehabilitation after anterior cruciate ligament reconstruction [26].
• The appropriate use of some supplements can benefit the athlete, but others may harm the athlete’s health, performance, and/or livelihood and reputation if an antidoping rule violation results [12].

What the Evidence Shows

Perioperative and Postoperative Supplementation

• Intravenous protein or amino acid supplementation offers benefits for total joint arthroplasty, while effects on muscle strength and function are mixed [3].
• Integrating targeted nutrition into prehabilitation pathways may help reduce complications and support faster functional gains in total joint arthroplasty [21].
• 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 [24].
• A comprehensive balanced nutrition supplement resulted in lower complication rates and mortality at 120 days postoperatively for hip fracture patients [31].
• The use of a low-cost commercially available amino acid supplement resulted in fewer overall complications postoperatively and was a low-risk intervention for the patient population [19].
• 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 [20].
• Nutrition consultation and perioperative supplementation with amino acids and micronutrients are 2 readily available interventions that orthopaedic surgeons can select for malnourished patients [11].
• 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 after anterior cruciate ligament reconstruction [5].
• Specific nutritional supplementation alone might benefit geriatric patients, especially relevant for those who are unable to exercise [2].

Osteoarthritis and Joint Health

• The excellent safety profile of glucosamine and chondroitin sulfate should be discussed with patients, and they may serve a role as an initial treatment modality for many OA patients [4].
• Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with osteoarthritis [6].
• The evidence supports efficacy of non-steroidal anti-inflammatory drugs and glucosamine sulfate in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis [7].
• Supplementation with omega-3 PUFAs for 3-4 months reduces patient reported joint pain intensity, minutes of morning stiffness, number of painful and/or tender joints, and NSAID consumption [8].
• Glucosamine sulfate has potential to relieve pain and improve function with low side effects, but unanswered questions regarding long-term effects and dosage preclude a definitive endorsement [10].
• If the cost is not prohibitive, glucosamine and chondroitin sulfate products may be considered reasonable treatment options as part of a multimodal approach for symptomatic primary hand osteoarthritis [14].
• Oral chondroitin is more effective than placebo on relieving pain and improving physical function, while glucosamine showed effect on stiffness outcome in osteoarthritis [33].
• Collagen peptides demonstrate significant pain relief in patients with knee osteoarthritis compared to those who received placebo [27].
• An 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 [25].

Cartilage and Tendon Injuries

• EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries [16].
• Treatment with hydrolyzed collagen was effective in reducing pain and supporting functional recovery in patients with rotator cuff tendinopathy, with effects observed after the first injection and persisting up to six months [29].

Sports Medicine and General Considerations

• With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute resistance training-induced gains in fat-free mass [18].
• Patients do not benefit from creatine supplementation during the first 12 weeks of rehabilitation after ACL reconstruction [26].
• Substantial barriers like inconsistent protocols and patient nonadherence remain for nutritional optimization in spine surgery, highlighting the need for multifactorial assessment and standardization of multidisciplinary nutritional protocols [22].

Practical Considerations

Perioperative and Postoperative Supplementation

• 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 [9].
• A low-cost commercially available amino acid supplement resulted in fewer overall complications postoperatively and was a low-risk intervention for the patient population [19].
• Protein supplementation is a low-cost intervention that is easy to incorporate into perioperative management for total knee arthroplasty [20].
• The beneficial effects of protein supplementation on muscle strength after total knee arthroplasty could potentially reduce the risk of longer-term complications, such as falls and periprosthetic fracture [20].
• 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 [22].

Osteoarthritis and Joint Health

• The excellent safety profile of glucosamine and chondroitin sulfate should be discussed with patients, and they may serve a role as an initial treatment modality for many osteoarthritis patients [4].
• The lack of substantial evidence currently prevents a ringing endorsement of glucosamine and chondroitin sulfate for osteoarthritis management [10].
• Evidence supports the efficacy of glucosamine sulfate in reducing pain, improving function, and possibly regulating joint damage in knee osteoarthritis [7].
• If the cost is not prohibitive, glucosamine and chondroitin sulfate may be considered reasonable treatment options as part of a multimodal approach for symptomatic primary hand osteoarthritis [14].
• Supplementation of n-3 polyunsaturated fatty acids (PUFAs) is effective to relieve pain and improve joint function in patients with osteoarthritis [6].
• EPA supplementation could offer a promising strategy for preventing post-traumatic osteoarthritis (PTOA) progression following acute cartilage injuries [16].

Musculoskeletal Recovery and Sarcopenia

• Specific nutritional supplementation alone might benefit geriatric patients, especially those who are unable to exercise, as shown by proof-of-principle in a vitamin D and leucine-enriched whey protein study [2].
• With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute to resistance training-induced gains in fat-free mass in healthy adults [18].

General and Sports Medicine Considerations

• Because of the lack of robust efficacy and safety data, peptide supplements should not currently be recommended as a replacement or adjunct for existing orthopaedic standard of care [1].

Key Evidence

• [L5] Because of the lack of robust efficacy and safety data, peptide supplements should not currently be recommended as a replacement or adjunct for existing orthopaedic standard of care. [1] (10.1177/03635465261464420)
• [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. [2] (10.1016/j.jamda.2015.05.021)
• [L1] While effects on muscle strength and function are mixed, intravenous supplementation offers benefits. [3] (10.1186/s13018-025-05847-4)
• [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. [4] (10.1016/j.arthro.2008.07.020)
• [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. [5] (10.1177/2325967118s00040)
• [L1] Supplementation of n-3 PUFAs is effective to relieve pain and improve joint function in patients with OA. [6] (10.1186/s13018-023-03855-w)
• [L4] The evidence supports efficacy in reducing pain, improving function, and possibly regulating joint damage. [7] (10.1186/s12891-022-06046-6)
• [L1] Supplementation with omega-3 PUFAs for 3-4 months reduces patient reported joint pain intensity, minutes of morning stiffness, number of painful and/or tender joints, and NSAID consumption. [8] (10.1016/j.pain.2007.01.020)
• [L1] CEAA supplementation has a protective effect against common complications and early skeletal muscle wasting after operative fixation of extremity and pelvic fractures. [9] (10.2106/jbjs.21.01014)
• [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] (10.5435/00124635-200109000-00009)
• [L5] Nutrition consultation and perioperative supplementation with amino acids and micronutrients are 2 readily available interventions that orthopaedic surgeons can select for malnourished patients. [11] (10.2106/jbjs.rvw.23.00242)
• [Paper] The appropriate use of some supplements can benefit the athlete, but others may harm the athlete’s health, performance, and/or livelihood and reputation (if an antidoping rule violation results). [12] (10.1136/bjsports-2018-099027)
• [L4] Nutritional supplementation has been shown to markedly reduce hospital costs by reducing rates of ICU admissions, hospital-associated complications, and hospital-acquired infections. [13] (10.5435/jaaos-d-23-00300)
• [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. [14] (10.1016/j.jhsa.2013.05.017)
• [L5] Our recommendations for data capture relating to female athlete population characteristics, and injuries, illnesses and other health consequences, will improve the quality of epidemiological studies, to inform better injury and illness prevention strategies. [15] (10.1136/bjsports-2022-106620)
• [L5] The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. [16] (10.1186/s13018-024-05081-4)
• [L1] However, oral nutritional supplementation and dietetic assistance represent low-risk interventions that may improve morbidity and mortality. [17] (10.1097/corr.0000000000000658)
• [L1] With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM. [18] (10.1136/bjsports-2017-097608)
• [L5] The use of the low-cost commercially available amino acid supplement resulted in fewer overall complications postoperatively and was a low-risk intervention for their patient population. [19] (10.2106/jbjs.22.00078)
• [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. [20] (10.2106/jbjs.22.01357)
• [L4] Integrating targeted nutrition into prehabilitation pathways may help reduce complications and support faster functional gains. [21] (10.1016/j.arth.2026.03.088)
• [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. [22] (10.5435/jaaos-d-25-00757)
• [L4] Perioperative nutritional optimization has been associated with improved outcomes for patients undergoing spine surgery, but additional investigation is needed to determine effective perioperative nutritional protocols. [23] (10.5435/jaaos-d-24-01101)
• [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. [24] (10.1177/2325967123s00326)
• [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. [25] (10.1186/s12891-024-08244-w)
• [L1] The results demonstrate that patients do not benefit from creatine supplementation during the first 12 weeks of rehabilitation after ACL reconstruction. [26] (10.1177/0363546503261731)
• [L1] Our findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. [27] (10.1186/s13018-023-04182-w)
• [L4] The treatment with hydrolyzed collagen was effective in reducing pain and supporting functional recovery in patients with rotator cuff tendinopathy, with effects observed after the first injection and persisting up to six months. [29] (10.1016/j.jseint.2023.06.009)
• [L1] Perioperative essential amino acid supplementation prevents rectus femoris muscle atrophy and accelerates early functional recovery after total knee arthroplasty. [30] (10.1302/0301-620x.102b6.bjj-2019-1370.r1)
• [L1] The comprehensive balanced nutrition supplement resulted in lower complication rates and mortality at 120 days postoperatively. [31] (10.1097/01.blo.0000224054.86625.06)
• [L5] This might indicate that GlcN exerts its potential analgesic properties through stimulation of synovial HA production. [32] (10.1186/1471-2474-9-120)
• [L1] Oral chondroitin is more effective than placebo on relieving pain and improving physical function, while glucosamine showed effect on stiffness outcome. [33] (10.1186/s13018-018-0871-5)

References

[1] Peptide Supplements and Their Therapeutic Applications in Sports Medicine. The American Journal of Sports Medicine. 2026. DOI: 10.1177/03635465261464420

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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

[8] A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007. DOI: 10.1016/j.pain.2007.01.020

[9] 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

[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] The Role of Perioperative Nutritional Status and Supplementation in Orthopaedic Surgery. JBJS Reviews. 2024. DOI: 10.2106/jbjs.rvw.23.00242

[12] IOC consensus statement: dietary supplements and the high-performance athlete. British Journal of Sports Medicine. 2018. DOI: 10.1136/bjsports-2018-099027

[13] 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

[14] Glucosamine and Chondroitin Sulfate Treatment of Hand Osteoarthritis. The Journal of Hand Surgery. 2013. DOI: 10.1016/j.jhsa.2013.05.017

[15] Female athlete health domains: a supplement to the International Olympic Committee consensus statement on methods for recording and reporting epidemiological data on injury and illness in sport. British Journal of Sports Medicine. 2023. DOI: 10.1136/bjsports-2022-106620

[16] 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

[17] Cochrane in CORR®: Nutritional Supplementation for Hip Fracture Aftercare in Older People. Clinical Orthopaedics & Related Research. 2019. DOI: 10.1097/corr.0000000000000658

[18] 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. British Journal of Sports Medicine. 2017. DOI: 10.1136/bjsports-2017-097608

[19] Essential Amino Acid Supplementation: Feed the Injured Patient. Journal of Bone and Joint Surgery. 2022. DOI: 10.2106/jbjs.22.00078

[20] 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

[21] Perioperative Nutritional Optimization in Total Joint Arthroplasty: From Screening to Supplementation. The Journal of Arthroplasty. 2026. DOI: 10.1016/j.arth.2026.03.088

[22] 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

[23] Perioperative Nutritional Optimization in Spine Surgery. Journal of the American Academy of Orthopaedic Surgeons. 2025. DOI: 10.5435/jaaos-d-24-01101

[24] Poster 363: Post-Operative Protein Supplementation following Orthopaedic Surgery: A Systematic Review. Orthopaedic Journal of Sports Medicine. 2023. DOI: 10.1177/2325967123s00326

[25] 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

[26] 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

[27] 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

[29] Subacromial injection of hydrolyzed collagen in the symptomatic treatment of rotator cuff tendinopathy: an observational multicentric prospective study on 71 patients. JSES International. 2023. DOI: 10.1016/j.jseint.2023.06.009

[30] 2020 Chitranjan S. Ranawat Award: Perioperative essential amino acid supplementation suppresses rectus femoris muscle atrophy and accelerates early functional recovery following total knee arthroplasty. The Bone & Joint Journal. 2020. DOI: 10.1302/0301-620x.102b6.bjj-2019-1370.r1

[31] Nutritional Supplementation Decreases Hip Fracture-related Complications. Clinical Orthopaedics and Related Research. 2006. DOI: 10.1097/01.blo.0000224054.86625.06

[32] Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants. BMC Musculoskeletal Disorders. 2008. DOI: 10.1186/1471-2474-9-120

[33] 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