Comparative efficacy of a standardized herbal composition LN22199, nicotinamide riboside, and their combination on NAD+ metabolism in healthy aging adults

Nicotinamide adenine dinucleotide (NAD+) depletion contributes to mitochondrial dysfunction, inflammation, cognitive and physical decline with aging, partly driven by upregulated cluster of differentiation 38 (CD38) activity. This 60-day randomized, double-blind, placebo-controlled trial evaluated LN22199, a polyphenol-rich blend of Punica granatum and Tagetes erecta, alone or with nicotinamide riboside (NR), in 140 healthy aging adults (age: 60.09 ± 4.20 years; male: female 59 %: 41 %). Participants received either a placebo, NR (500 mg), LN22199 (1000 mg), or LN22199 (500 mg) + NR (500 mg). Outcomes included NAD+ levels, CD38 activity, inflammatory biomarkers, cognitive function, physical performance, and quality-of-life measures. LN22199 increased blood NAD+ levels by 26.48 %, NR by 22.69 %, and their combination by 31.76 % (all p < 0.001 vs. baseline). CD38 activity decreased significantly with LN22199 alone (17.98 % reduction, p = 0.0025 vs. baseline; p = 0.0344 vs. placebo), while NR alone showed minimal change. Serum growth/differentiation factor 15 (GDF-15) levels declined by 15.07 % (LN22199; p = 0.0001), 11.36 % (NR; p = 0.0033), and 17.83 % (combination; p < 0.0001) vs. baseline. The combination group achieved the greatest improvements in functional outcomes, including a 9.94 % increase in six-minute walk distance and a 16.45 % improvement in Mini-Mental State Examination 2 cognitive scores. All treatments were well tolerated with no serious adverse events reported. LN22199, combined with NR, enhances NAD+ homeostasis, mitigates inflammation, and improves cognitive and physical function, representing a promising strategy for healthy aging.