Safety and immune-supportive potential of the food supplement 5-aminolevulinic acid phosphate for patients with COVID-19: An open-label, non-randomized pilot study

Background: One mode of action of 5-ALA with SFC is the induction of Heme Oxygenase-1, a key regulator in anti-oxidative and immunological processes, leading to the hypothesis that the product supports faster recovery from infections such as COVID-19. Objective: The main objective was to assess the safety and immune-supportive potential of the food supplement 5-aminolevulinic acid phosphate (5-ALA) with sodium ferrous citrate (SFC) in patients with COVID-19 when co-administered with standard of care medications (SoC).Methods: A patient group with moderate COVID-19 symptoms (four males and three females, mean age 43 years) and one group with severe symptoms (12 males, mean age 48 years) received daily oral doses of 500 mg/750 mg 5-ALA with 286 mg/430 mg SFC for the first 7 days (≤7.5 times higher than the recommended dose for the marketed product). For the subsequent 21 d, the daily dose was reduced to 250 mg 5-ALA with 143 mg SFC in both groups. Adverse events and several immunological laboratory parameters were collected. Moreover, the mean hospital stay was compared with historical data of patients solely treated with SoC. Results: Two patients in the moderate group showed elevated liver enzymes; however, these seemed to be related to SoC. In the severe group, one patient experienced constipation. No serious adverse events were observed. In the severe group, a significant decrease of C-reactive protein (109.42 5.41 mg/L; p <0.005), procalcitonin (0.87 to 0.07 ng/mL; p <0.005), and interleukin 6 (20.07 to 5.06 pg/mL; p <0.05) and an increase of the cluster of differentiation 4 (250 to 880 cells/µl; p <0.05) and the cluster of differentiation 8 (190 to 623 cells/µL; p <0.05) were detected. The hospital stay of the severe group was markedly shorter (8 d only) than that of the control group (16 d).Conclusions: 5-ALA with SFC was evaluated as safe for administration in COVID-19 patients. Moreover, there were signals detecting its immune-supportive potential. The small number of included patients limits interpretation of the significance of the results; however, the study is useful in deciding future development strategies. Trial Registration: The study was registered on ClinicalTrials.gov (https://clinicaltrials.gov/) on September 06, 2020 (registration no. NCT04542850.Keywords: 5-aminolevulinic acid; COVID-19; SARS-CoV-2; food supplement