Fermented Noni Polysaccharides Boost NK Cell Activity in Adults with Recurrent URTIs

Recurrent Upper Respiratory Tract Infections (URTIs) pose a significant burden, particularly in aging populations, often leading to reduced quality of life and increased healthcare utilization. Current symptomatic treatments do not address underlying immune deficiencies that contribute to susceptibility. Modulating innate immune responses, specifically enhancing Natural Killer (NK) cell activity, represents a promising strategy to bolster the body's first line of defense against viral and bacterial pathogens. Polysaccharides from Morinda citrifolia (noni) have shown immunomodulatory potential in preclinical studies, but robust clinical evidence for their efficacy in human immune function, especially in the context of recurrent infections, has been limited.

This randomized, double-blind, placebo-controlled trial enrolled 100 adults (aged 40 to <75 years) with a history of ≥2 URTIs in the prior 12 months. Participants were randomly assigned to receive either fermented noni polysaccharides (FNP) at a dose of 975 mg/day (two 487.5 mg tablets once daily) or a matched placebo for 8 weeks. The primary endpoint was the change in NK cell activity from baseline, measured using K562 NK-sensitive target cells at effector-to-target (E:T) ratios of 50:1, 25:1, and 12.5:1. Secondary endpoints included changes in circulating cytokines (IFN-γ, TNF-α, IL-2, IL-6, IL-10, IL-12, IL-1β) and immunoglobulin G (IgG) levels. Primary efficacy analysis was conducted on the modified intention-to-treat/full analysis set (mITT/FAS) of 84 participants.

In the treatment group, NK cell activity consistently increased from baseline across all three E:T ratios, while the placebo group showed a slight decrease. For the primary endpoint in the mITT/FAS, adjusted between-group LS mean differences (95% CI) favored the fermented noni polysaccharides group but did not reach conventional statistical significance: +8.94 (-0.61, 18.50; p = 0.066) at E:T 50:1, +7.68 (-1.14, 16.50; p = 0.087) at E:T 25:1, and +3.29 (-2.95, 9.54; p = 0.145) at E:T 12.5:1. However, prespecified per-protocol set (PPS) sensitivity analyses, which included 81 participants (41 FNP, 40 placebo), revealed a statistically significant increase in NK cell activity at the highest E:T ratio.

At an E:T ratio of 50:1, the PPS analysis showed an 11.03% greater increase in NK cell activity in the fermented noni polysaccharides group compared to placebo (p = 0.025). This suggests a robust effect under optimal adherence. No specific results for secondary cytokine or IgG endpoints were detailed in the abstract.