Efficacy of Cordyceps cicadae (Ascomycota) Mycelium Supplementation for Amelioration of Dry Eye Symptoms: A Randomized, Double-Blind Clinical Pilot Study

Dry eye disease (DED), a multifactorial inflammatory ocular surface disorder, affects up to 50% of individuals over 50 years old worldwide and is one of the most common reasons for seeking ophthalmologic care. Generally, topical eye drops or oral drugs are administered to treat DED; however, the use of preservatives in eye drops or the adverse effects of oral drugs are disadvantageous for long-term therapy. Cordyceps cicadae, a traditional Chinese medicinal fungus, possesses anti-inflammatory effects without evident toxicity and is obtainable at low price. Our previous study demonstrated that C. cicadae mycelium effectively ameliorates dry eye symptoms in the benzalkonium chloride (BAC)-induced mouse dry eye model by increasing tear volume and tear film breakup time (TBUT). However, the effects of C. cicadae mycelium for human dry eye amelioration remains unknown. Thus, the present study investigated the mitigation of dry eye conditions and related discomforts through oral supplementation of fermented C. cicadae mycelium. A total of 70 healthy individuals were recruited and randomly allocated to receive a daily oral dose of 1,050 mg preparation in sachet containing either freeze-dried C. cicadae mycelium powder with 0.3 mg of adenosine and 1.5 mg of HEA per gram or placebo for 90 days. The participants were subjected to anthropometric measurements, dry eye questionnaires (DEQ), Schirmer's tests, intraocular pressure (IOP) measurements, tear film breakup time (TBUT) tests, tear osmolality measurements, and tear electrolyte analysis prior to and right after completion of the study. The results showed a significantly increased TBUT as well as a significant decrease in tear osmolarity, in parallel with the decrease of tear electrolytes, especially Na+ and Cl ions. Although significant increase of tear volume was not observed, the increased TBUT suggests mitigation of dry eye through improvement of tear quality. Therefore, C. cicadae mycelium supplementation may be used for dry eye alleviation as a novel therapeutic intervention.