What supplements help with post-COVID inflammation?
Executive summary
Post‑COVID (long COVID) inflammation is a heterogeneous, low‑grade immune activation that researchers have targeted with dietary strategies and supplements; some agents — notably vitamin D, omega‑3 fatty acids, glutathione precursors/N‑acetylcysteine, quercetin, zinc and combined vitamin K2/D3 — show mechanistic rationale and mixed clinical signals, but robust, large randomized evidence remains limited [1] [2] [3]. Clinical guidance emerging from reviews is pragmatic: correct true deficiencies, prioritize an anti‑inflammatory diet (Mediterranean pattern), and consider specific supplements for patients with documented deficits or when small trials suggest benefit, while remaining alert to safety and interactions [1] [4] [5].
1. What clinicians and reviews mean by “post‑COVID inflammation” — why supplements are considered
Long COVID commonly involves persistent symptoms thought to reflect ongoing immune dysregulation, low‑grade systemic inflammation, oxidative stress and tissue repair needs, which has prompted researchers to test nutrients and nutraceuticals that modulate cytokines, antioxidant systems and mucosal/vascular integrity [1] [6]. Dietary and supplementation recommendations in systematic reviews therefore frame interventions as ways to reduce pro‑inflammatory cytokines, correct deficiencies that worsen inflammation, or support resolution pathways rather than as cures for the syndrome itself [1] [4].
2. Vitamin D and K: the strongest, most studied micronutrient pair
Vitamin D has been repeatedly associated with inflammation indices and COVID outcomes in observational work and small trials, and is recommended for people who are deficient because it shifts T‑cell responses and can reduce pro‑inflammatory cytokines; combined vitamin K2/D3 supplementation produced a randomized trial signal of reduced inflammation in long COVID in a 2025 MDPI RCT [2] [7] [3]. Reviews recommend correcting low 25‑OH vitamin D in post‑COVID patients, but emphasize that blanket megadosing without testing is not supported by high‑quality evidence [1] [2].
3. Omega‑3s and specialized pro‑resolving mediators: inflammation resolution, not immune suppression
Omega‑3 polyunsaturated fatty acids have long mechanistic plausibility for reducing pro‑inflammatory mediators and promoting resolution of inflammation; clinical reviews and trials in related inflammatory lung conditions and post‑COVID contexts justify ongoing trials and cautious use, though there are debated risks (e.g., bleeding, oxidation of supplements) and the need to pair with antioxidants in some formulations [5] [4] [8].
4. Antioxidants and glutathione precursors (NAC), inositol and cysteine‑based strategies
Oxidative stress is a candidate driver of lingering symptoms; glutathione supplementation and precursors such as N‑acetylcysteine improve markers of oxidative damage in tissues in several studies and are suggested as strategy components alongside inositol in post‑COVID nutritional reviews [9] [1] [6]. Evidence is largely mechanistic or from small trials, so these remain promising but not definitive clinical standards [9] [6].
5. Quercetin, zinc, melatonin and other nutraceuticals — mixed signals from small trials
Quercetin, a plant flavonoid, has shown anti‑inflammatory activity (NF‑κB pathways) and some interim RCT results suggesting faster viral clearance and reduced symptom severity in acute COVID, with investigators exploring its role in early long‑COVID phases; zinc has observational links to worse inflammation when low and is commonly used where deficiency is suspected [2] [4]. Melatonin and CBD/terpenes are under investigation for inflammasome and neuroimmune effects but the clinical evidence base remains preliminary [5] [2].
6. Practical clinical approach and caveats
Major reviews recommend prioritizing dietary patterns rich in anti‑inflammatory foods (Mediterranean diet), testing for and correcting deficiencies (vitamin D, zinc, protein/muscle‑supporting amino acids) and using supplements selectively for malnourished patients or when small RCTs support benefit; clinicians should weigh interactions (e.g., omega‑3 and bleeding risk) and individual comorbidities before starting supplements [1] [4] [5]. Large, definitive randomized trials remain sparse, so personalized, evidence‑informed decisions and medical supervision are essential [2] [1].