Plant stanol consumption increases anti-COVID-19 antibody responses, independent of changes in serum cholesterol concentrations: a randomized controlled trial

BACKGROUND: People with overweight/obesity generally have impaired immune responses, resulting amongst others in an increased risk of severe complaints and hospitalization after infections with severe acute respiratory syndrome coronavirus 2 (COVID-19, SARS-COV-2), as well as decreased antibody production after vaccinations. Plant stanol ester previously increased the combined immunoglobulin M and G (IgM/IgG) antibody titers towards a hepatitis A vaccination in allergic asthma patients, but the underlying mechanism is unknown. OBJECTIVE: We evaluated whether plant stanol ester consumption improved the immune response in subjects with overweight/obesity after a COVID-19 vaccination. METHODS: A double-blind, randomized, placebo-controlled trial was performed (registered at clinicaltrials.gov [NCT04844346]). Thirty-two subjects with overweight/obesity consumed products with added plant stanols (4g/day; provided as plant stanol ester) or control at least two weeks before receiving their COVID-19 vaccination until 4 weeks after vaccination. Antibody titers were analyzed weekly and statistically analyzed using mixed models. Serum metabolic markers and cytokine profiles were also analyzed. RESULTS: IgM concentrations against the COVID-19 spike protein were increased in the plant stanol ester group as compared to control , with the largest difference observed 2 weeks after vaccination (31.2 [0.43; 62.1] binding antigen units [BAU]/mL, or +139 %; Group*Time: p=0.031). Subjects that produced very low IgM antibodies produced as expected hardly any IgG antibodies. In those with IgG sero-conversion, IgG spike concentrations were also increased in the plant stanol ester group as compared to control (71.3 [2.51; 140.1] BAU/mL; Group p=0.043). Stimulated cytokine concentrations decreased in the plant stanol ester group compared to control in all three cytokine domains (i.e., pro-inflammatory, T helper [Th1]/Th17, Th2/regularory T cell [Treg]). Between-group differences in serum low-density lipoprotein (LDL) cholesterol or other metabolic markers were not observed. CONCLUSION: Consuming plant stanols (4g/day) affects immune responses to COVID-19 vaccinations, translating into increased serum anti-COVID-19 IgM concentrations in subjects with overweight/obesity. Only in IgG seroconverted subjects, serum anti-COVID-19 IgG concentrations also increased. These effects were independent of reductions in LDL cholesterol. These results suggest that this high-risk group for COVID-19 complications could benefit from plant stanol consumption. Clinical Trial Registry website and number: clinicaltrials.gov, NCT04844346.