Nutritional Supplements for Knee Surgery Recovery

Overseen By Danielle Nyman, PhD(c)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Dr. Chris McGlory, PhD

Must not be taking: Fish oils, Steroids

Disqualifiers: Cancer, Bleeding disorders, Pregnancy, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking fish oils, steroids, or certain blood thinners. It's best to discuss your specific medications with the trial team.

What evidence supports the effectiveness of the treatment Omega-3 Fatty Acids and Essential Amino Acids for knee surgery recovery?

Research shows that omega-3 fatty acids can help reduce inflammation and muscle weakness after surgery, which may aid in recovery. Specifically, they have been found to lessen quadriceps weakness after knee surgery and improve overall surgical outcomes by reducing inflammation. ^{1 2 3 4 5}

Is it safe to use omega-3 fatty acids and essential amino acids for surgery recovery?

Research suggests that omega-3 fatty acids are generally safe for use in humans, including surgical patients, and may even offer benefits like reduced inflammation and shorter hospital stays. Prescription formulations of omega-3 fatty acids have been tested in clinical trials and are considered safe at FDA-approved dosages. ^{1 5 6 7 8}

How is the treatment of Omega-3 Fatty Acids and Essential Amino Acids for knee surgery recovery different from other treatments?

This treatment is unique because it uses Omega-3 fatty acids, which have anti-inflammatory and antioxidant effects, potentially reducing muscle weakness after knee surgery. Unlike other treatments, it focuses on improving recovery by modulating inflammation and oxidative stress, which are common after surgery. ^{1 2 5 7 9}

What is the purpose of this trial?

Loss of skeletal muscle mass (atrophy) and strength in the lower limb are consequences of elective knee surgery as result of prolonged disuse from limb immobilization and impaired mobility, as well as pathophysiological trauma. The highest rates of skeletal muscle mass and strength loss occur during the 2-week post-surgery period, considered the early phase of outpatient recovery. Alternative to resistance exercise and pharmacology, nutritional intervention represents one strategy to combat skeletal muscle disuse atrophy. Essential amino acids (EAA) and omega-3 fatty acids are known to independently potentiate rates of skeletal muscle protein synthesis and attenuate skeletal muscle atrophy in humans. However, the combined actions these nutritional strategies on skeletal muscle have not been explored in a pathophysiological context, such as surgery. With the ultimate goal to test the efficacy of the combined nutritional strategy to attenuate skeletal muscle disuse atrophy in the future, the aim of this present pilot study is to explore the feasibility of recruitment and retention of anterior cruciate ligament reconstruction (ACLR) outpatients from a single centre across 18 months for a 6-week nutritional intervention. Participants will consume either an intervention of omega-3 fatty acids and EAAs, or a placebo control of safflower oil and non-essential amino acids (NEAA), for 4 weeks before and 2 weeks after elective ACLR surgery. Furthermore, this pilot will characterize secondary outcomes of skeletal muscle mass, strength, and power, and integrated rates of muscle protein synthesis, as well as report participant adherence to protocols and incidence of adverse events.

Research Team

Chris McGlory, PhD

Principal Investigator

Queen's University

Eligibility Criteria

This trial is for adults with a diagnosed anterior cruciate ligament injury who are scheduled for reconstruction surgery using patellar or quadriceps tendon grafts in Kingston, ON. It's designed to see if certain nutritional supplements can help prevent muscle loss after knee surgery.

Inclusion Criteria

I need surgery for a torn ACL in my knee.

My surgery will be in Kingston, ON.

I had knee surgery using a patellar or quadriceps tendon graft.

Exclusion Criteria

I do not have any illnesses that prevent me from following study procedures.

Pregnant or plans to become pregnant within the next 6 months

I do not have any health conditions that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgery Nutritional Intervention

Participants receive omega-3 fatty acids and EAAs or placebo for 4 weeks before surgery

4 weeks

1 visit (in-person) for baseline measurements

Post-Surgery Nutritional Intervention

Participants continue receiving omega-3 fatty acids and EAAs or placebo for 2 weeks after surgery

2 weeks

1 visit (in-person) for post-surgery assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

2 visits (in-person) for follow-up assessments

Treatment Details

Interventions

• Omega-3 Fatty Acids and Essential Amino Acids

Trial Overview The study tests whether taking omega-3 fatty acids and essential amino acids can reduce muscle atrophy compared to a control group taking safflower oil and non-essential amino acids. Participants will start the supplements 4 weeks before surgery and continue for 2 weeks after.

Participant Groups

Group I: Nutritional Intervention Experimental Treatment 1 Intervention

5 g omega-3 fatty acids (3.75 g eicosapentaenoic acid \[EPA\] + 1.25 g docosahexaenoic acid \[DHA\]) per day for 6 weeks, starting 4 weeks before and continuing 2 weeks after surgery, plus 40 g (2 x 20 g) of EAA per day, starting 1 week before and continuing 2 weeks after surgery.

Group II: Placebo Control Placebo Group 1 Intervention

5 g safflower oil per day for 6 weeks, starting 4 weeks before and continuing 2 weeks after surgery, plus 40 g (2 x 20 g) of NEAA per day, starting 1 week before and continuing 2 weeks after surgery.

Omega-3 Fatty Acids and Essential Amino Acids is already approved in United States, European Union for the following indications:

Approved in United States as Omega-3 fatty acids for:

• Hypertriglyceridemia
• Cardiovascular health

Approved in European Union as Omega-3 fatty acids for:

• Hypertriglyceridemia
• Cardiovascular health
• Inflammation

Approved in United States as Essential Amino Acids for:

• Nutritional supplement
• Muscle recovery

Approved in European Union as Essential Amino Acids for:

• Nutritional supplement
• Muscle recovery
• Wound healing

Who Is Running the Clinical Trial?

Dr. Chris McGlory, PhD

Lead Sponsor

Trials

3

Recruited

80+

Dr. Chris McGlory, PhD

Lead Sponsor

Trials

3

Recruited

80+

Findings from Research

In a study involving 148 patients undergoing colorectal cancer surgery, an omega-3 fatty acid (n-3 FA) enriched supplement significantly increased levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) in granulocytes compared to a standard supplement.

Despite the successful incorporation of n-3 FAs into immune cells, there was no significant difference in postoperative complications or hospital stay between the n-3 FA group and the control group, indicating that higher levels of these fatty acids did not lead to improved surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery. Sorensen, LS., Thorlacius-Ussing, O., Schmidt, EB., et al.[2016]

Preoperative supplementation with n-3 long-chain polyunsaturated fatty acids significantly reduced quadriceps weakness in patients after total knee arthroplasty, suggesting a beneficial effect on muscle strength recovery.

The intervention increased the beneficial eicosapentaenoic acid and docosahexaenoic acid levels relative to arachidonic acid, although it did not significantly affect oxidative stress, swelling, or pain levels post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of n-3 polyunsaturated fatty acid supplementation on quadriceps weakness immediately after total knee arthroplasty: a pilot, randomized, open-label clinical trial. Kubo, Y., Ikeya, M., Sugiyama, S., et al.[2023]

Preoperative administration of omega-3 fatty acids did not show a significant effect on postoperative inflammatory markers (CRP, IL-6, WBC) or length of hospital stay in patients undergoing abdominal surgery, based on a meta-analysis of 13 randomized controlled trials involving 950 patients.

Although some reductions in inflammatory markers were noted, the overall results were inconclusive, suggesting that more extensive research is needed to clarify the impact of omega-3 fatty acids on postoperative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Omega-3 Fatty Acids on Postoperative Inflammatory Response: A Systematic Review and Meta-Analysis. Mohsen, G., Stroemer, A., Mayr, A., et al.[2023]

In a study involving 100 patients undergoing colon or liver surgery, the MOFA program, which included omega-3 fatty acids and glucose control, resulted in earlier flatulence but did not significantly improve the time to the first bowel movement compared to standard ERAS therapy.

The MOFA approach did not show any negative effects on coagulation or inflammation, and there were no significant differences in hospital stay or postoperative complications, suggesting that while it may have some benefits, it does not enhance recovery outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a metabolic optimized fast track concept (MOFA) on bowel function and recovery after surgery in patients undergoing elective colon or liver resection: a randomized controlled trial. Uhlig, C., Rössel, T., Denz, A., et al.[2020]

n-3 polyunsaturated fatty acids may help reduce inflammation in surgical patients by influencing inflammatory mediators and cell membrane interactions, potentially leading to better recovery outcomes.

Clinical trials suggest that n-3 fatty acids can improve key outcomes such as shorter hospital stays, fewer infections, and lower mortality rates in patients undergoing surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effects of the n-3 long-chain polyunsaturated fatty acids in surgical patients: updating the evidence. Bernabe-Garcia, M., Lopez-Alarcón, M., Blanco-Favela, F., et al.[2011]

Supplementation with Omega-3 fatty acids (EPA + DHA) significantly increases the Omega-3 Index (O3Ix) in red blood cells of elite athletes over 4 months, with a dose-dependent response observed in both 760 mg and 1140 mg groups.

The majority of athletes (93.1%) had low baseline O3Ix levels, and those with lower initial levels showed the greatest increase in Omega-3 content, indicating that supplementation is particularly beneficial for athletes starting with lower Omega-3 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythrocyte Omega-3 Fatty Acid Content in Elite Athletes in Response to Omega-3 Supplementation: A Dose-Response Pilot Study. Drobnic, F., Rueda, F., Pons, V., et al.[2020]

In a study of 148 patients undergoing elective colorectal cancer surgery, an n-3 fatty acid-enriched nutritional supplement significantly increased anti-inflammatory markers (LTB5 and 5-HEPE) and decreased pro-inflammatory markers (LTB4) compared to a standard supplement.

Despite these anti-inflammatory effects, the use of n-3 fatty acids did not lead to a reduction in postoperative complications, suggesting that while they may modulate immune response, they do not impact surgical recovery outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of perioperative supplementation with omega-3 fatty acids on leukotriene B₄ and leukotriene B₅ production by stimulated neutrophils in patients with colorectal cancer: a randomized, placebo-controlled intervention trial. Sorensen, LS., Thorlacius-Ussing, O., Rasmussen, HH., et al.[2021]

Prescription omega-3-acid ethyl esters (P-OM3) have been shown to be safe and effective in clinical trials, providing clear evidence for their use, unlike many dietary supplement forms of omega-3 fatty acids.

Clinical guidelines based on evidence now support the use of P-OM3, helping to clarify misconceptions and concerns about omega-3 fatty acids in medical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dispelling the myths about omega-3 fatty acids. Sadovsky, R., Collins, N., Tighe, AP., et al.[2008]

In a study involving 1,398 adults with chronic knee pain, neither vitamin D nor marine Omega-3 fatty acids (n-3 FA) showed any significant effect on reducing knee pain over an average follow-up of 5.3 years.

The results indicate that supplementation with vitamin D and n-3 FA does not improve knee function or stiffness, suggesting these treatments may not be effective for managing symptoms of osteoarthritis in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial. MacFarlane, LA., Cook, NR., Kim, E., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of perioperative omega-3 fatty acid supplements in elective colorectal cancer surgery. [2016]

2. Japan pubmed.ncbi.nlm.nih.gov

Effects of n-3 polyunsaturated fatty acid supplementation on quadriceps weakness immediately after total knee arthroplasty: a pilot, randomized, open-label clinical trial. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Omega-3 Fatty Acids on Postoperative Inflammatory Response: A Systematic Review and Meta-Analysis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Effects of a metabolic optimized fast track concept (MOFA) on bowel function and recovery after surgery in patients undergoing elective colon or liver resection: a randomized controlled trial. [2020]

5. Scotland pubmed.ncbi.nlm.nih.gov

Beneficial effects of the n-3 long-chain polyunsaturated fatty acids in surgical patients: updating the evidence. [2011]

6. Egypt pubmed.ncbi.nlm.nih.gov

Erythrocyte Omega-3 Fatty Acid Content in Elite Athletes in Response to Omega-3 Supplementation: A Dose-Response Pilot Study. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of perioperative supplementation with omega-3 fatty acids on leukotriene B₄ and leukotriene B₅ production by stimulated neutrophils in patients with colorectal cancer: a randomized, placebo-controlled intervention trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Dispelling the myths about omega-3 fatty acids. [2008]

9. United States pubmed.ncbi.nlm.nih.gov

The Effects of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial. [2022]