Polymethoxylated flavones (PMFs) are a unique class of flavonoids primarily found in citrus peels, especially in sweet orange and tangerine. Interest in PMFs for immune support is based on their anti-inflammatory and immunomodulatory properties demonstrated in preclinical studies. Laboratory research has shown that PMFs, such as nobiletin and tangeretin, can modulate immune cell activity, inhibit inflammatory cytokine production, and suppress the activation of pathways (like NF-κB) that are involved in immune responses. Some animal studies suggest that PMFs may enhance host resistance to pathogens and reduce markers of inflammation in models of immune dysfunction.

However, human clinical data are limited. Most evidence comes from in vitro and animal studies, with only a few small human trials examining PMFs for general health or metabolic support rather than specifically for immune enhancement. No major regulatory bodies have approved PMFs as immune-supportive agents, but their biological plausibility and early results are promising. The evidence base is stronger than tradition alone, as citrus peels have not been widely used for immune system support in traditional medicine, but the lack of extensive human data prevents a higher rating. More clinical research is needed to confirm efficacy and establish appropriate dosages for immune support.