What over-the-counter (OTC) supplements, such as ibuprofen (nonsteroidal anti-inflammatory drug (NSAID)) or acetaminophen (paracetamol), can a relatively healthy adult take to alleviate post-workout muscle soreness and inflammation?

Post-Workout Muscle Soreness Management

For post-workout body pain in healthy adults, topical NSAIDs (such as diclofenac gel) are the most effective first-line treatment, providing superior pain relief, functional improvement, and treatment satisfaction compared to oral medications, with significantly fewer systemic side effects. 1, 2

Primary Recommendation: Topical NSAIDs

Topical NSAIDs should be your first choice for post-workout muscle soreness based on the highest quality evidence from the American College of Physicians and American Academy of Family Physicians guidelines. 1

Why Topical NSAIDs Are Superior:

• Pain relief begins within 2 hours of application, with moderate-certainty evidence showing a reduction of 1.02 cm on a 10-cm pain scale 2
• Sustained relief continues for 1-7 days after application (pain reduction of 1.08 cm on 10-cm scale) 1, 2
• High-certainty evidence demonstrates superior treatment satisfaction compared to all other options (OR 5.20) 1
• Improved physical function with moderate-certainty evidence showing 1.66 cm improvement on functional scales 1
• Significantly fewer gastrointestinal side effects compared to oral NSAIDs, making them safer for regular use 2

Application Instructions:

• Apply topical diclofenac gel directly to the affected muscle groups 2
• Can be combined with menthol gel for enhanced pain relief (pain reduction of 1.68 cm within 2 hours) 2
• Dermatologic adverse events occur at rates similar to placebo 2

Second-Line Option: Oral NSAIDs (Ibuprofen)

If topical NSAIDs are insufficient or impractical for large muscle groups, oral NSAIDs like ibuprofen are the next best option. 1

Evidence for Oral NSAIDs:

• Moderate-certainty evidence shows pain reduction of 0.99 cm on a 10-cm scale at 1-7 days 1
• Improved physical function with 0.73 cm improvement on functional scales 1
• Symptom relief with moderate-certainty evidence (OR 3.10) 1

Critical Safety Considerations:

• Oral NSAIDs increase gastrointestinal adverse events with moderate-certainty evidence (OR 1.77) 1
• Risk of drug-drug interactions with other medications, particularly in those with hypertension, heart failure, or kidney disease 1, 3
• Should not be used in high doses for prolonged periods due to GI, platelet, and nephrotoxic effects 1
• Maximum over-the-counter dose is 1,200 mg/day (400 mg three times daily) 3

Important Caveat About Ibuprofen and Muscle Adaptation:

Research evidence reveals a significant concern: high doses of ibuprofen (1,200 mg/day) may suppress muscle protein synthesis after resistance exercise by 76% compared to placebo. 4 However, moderate doses (400 mg/day) do not impair muscle hypertrophy or strength gains during training. 5 This suggests that if you're using NSAIDs regularly for post-workout soreness, keep doses moderate (≤400 mg/day) to avoid interfering with training adaptations.

Third-Line Option: Acetaminophen

Acetaminophen is less effective than NSAIDs for post-workout pain but has a better safety profile. 1

Evidence for Acetaminophen:

• Moderate-certainty evidence shows pain reduction of 1.07 cm on a 10-cm scale at 1-7 days 1
• Does NOT improve physical function (low-certainty evidence showed no significant benefit) 1
• Does NOT improve symptom relief when used alone (moderate-certainty evidence) 1
• No gastrointestinal side effects unlike NSAIDs 1

Dosing and Safety:

• Maximum dose is 4,000 mg per day (can take 2 caplets every 8 hours, maximum 6 caplets in 24 hours) 6
• Should not exceed 10 days of continuous use without physician guidance 6
• Suppresses muscle protein synthesis similar to ibuprofen when taken at maximal doses (4,000 mg/day) after eccentric exercise 4

What Does NOT Work Well:

Based on the guideline evidence, avoid these common approaches: 1

• Acetaminophen plus ibuprofen combination: Low-certainty evidence shows no statistically significant pain reduction at early timepoints and no symptom relief benefit 1
• Muscle relaxants (cyclobenzaprine): Low-certainty evidence shows no benefit when combined with ibuprofen 1
• Glucosamine: Moderate-certainty evidence shows no pain reduction 1

Practical Algorithm for Post-Workout Pain:

1. Start with topical diclofenac gel applied to sore muscles 2-3 times daily 2
2. If pain involves large muscle groups or multiple areas, switch to oral ibuprofen 400 mg once daily (not three times daily to minimize interference with muscle adaptation) 5
3. If you have GI sensitivity or contraindications to NSAIDs, use acetaminophen up to 4,000 mg/day divided into doses every 8 hours 1, 6
4. Limit any pharmacologic treatment to 7-10 days maximum for routine post-workout soreness 6

Critical Pitfalls to Avoid:

• Do not use prophylactic NSAIDs before every workout if your goal is muscle hypertrophy, as this may interfere with training adaptations 4
• Do not combine multiple NSAIDs (e.g., oral plus topical from the same drug class simultaneously) without medical supervision 3
• Do not exceed maximum daily doses: ibuprofen 1,200 mg/day OTC, acetaminophen 4,000 mg/day 6, 3
• Do not use NSAIDs if you have active peptic ulcer disease, significant kidney disease, or heart failure 1, 3