Summary: In an open-label trial in diabetic foot osteomyelitis, adding oral N-acetylcysteine to standard antibiotics accelerated the fall in inflammatory markers (ESR and CRP) over three weeks, with mild gastrointestinal effects, though clinical outcomes like healing and amputation were not assessed.
PICO Summary
| Element | Detail |
|---|---|
| Population | 53 patients with diabetic foot osteomyelitis (Wagner grade III–IV); Iran. |
| Intervention | N-acetylcysteine 600 mg effervescent tablet twice daily for 2 weeks plus standard antibiotics. |
| Comparison | Standard antibiotic therapy alone. |
| Outcome | Greater reduction in infectious markers with NAC (ESR -49.44 vs -7.17; CRP -44.43 vs -14.02; both p<0.05), with most parameters improved except lymphocyte proportion and NLR (p=0.11, 0.84). Open-label design. |
NAC adjuvant therapy in diabetic foot osteomyelitis
Open-label RCT · diabetic foot osteomyelitis · 3 weeks
Adding NAC to antibiotics produced a faster fall in CRP and ESR over three weeks. Biomarker-only endpoints and open-label design mean healing, recurrence, and amputation remain unknown.
Expert Commentary
The rationale is appealing and biologically grounded: biofilm is a central reason diabetic foot osteomyelitis resists treatment, and N-acetylcysteine disrupts biofilm matrix and replenishes glutathione, so a faster inflammatory response when it is added to antibiotics fits the mechanism. It is also cheap, familiar, and well tolerated, which lowers the bar for trying it. But I read this as preliminary, for two honest reasons. First, the trial is open-label, and unblinded assessment of something as judgement-sensitive as response is vulnerable to bias. Second, and more importantly, the endpoints are biomarkers, ESR and CRP, not the outcomes that actually matter to a patient with infected bone: healing, recurrence, and amputation, none of which were reported. A faster fall in CRP is encouraging but is not the same as curing osteomyelitis. Can I use this with my patients? Cautiously and as an adjunct only. Given its safety and low cost, adding NAC to a proper regimen is defensible, but it must never substitute for appropriate antibiotics, debridement, offloading, vascular assessment, and glycaemic control. I would want a blinded trial with clinical endpoints before recommending it routinely.
References
Hooshmand Gharabagh L, Heydaroghli M, Esmaeili A. Efficacy of N-acetyl-cysteine as adjuvant therapy for diabetic foot osteomyelitis: an open-label randomized controlled trial. Arch Iran Med. 2025;28(5):257–263. doi:10.34172/aim.33355