Core Viewpoint - The article discusses a study comparing the effectiveness of three NAD+ supplements: Nicotinamide (Nam), Nicotinamide Riboside (NR), and Nicotinamide Mononucleotide (NMN), highlighting that NR and NMN significantly increase NAD+ levels in humans, while Nam does not show a significant difference compared to a placebo [2][3][9]. Group 1: Study Overview - The study was conducted by Nestlé Health Science and published in Nature Metabolism, focusing on the differential impacts of the three NAD+ boosters on human circulatory NAD+ levels and microbial metabolism [2][3][9]. - A total of 65 healthy participants were randomly assigned to four groups, receiving either NR (1000mg), NMN (1000mg), Nam (500mg), or a placebo for 14 days [9]. Group 2: Results - NR and NMN resulted in a doubling of NAD+ levels in participants, with increases of 49.4μM and 43.1μM respectively, while the Nam group showed no significant difference compared to the placebo group [9]. - The study indicates that the effectiveness of NR and NMN is due to their conversion to nicotinic acid (NA) by gut microbiota, leading to a sustained increase in NAD+ levels [11][12]. Group 3: Mechanism of Action - NR and NMN require gut microbiota for their metabolism, which ensures a gradual and stable increase in NAD+ levels, while Nam is rapidly absorbed, leading to transient effects [11][12]. - The research also highlights that NR and NMN not only enhance NAD+ levels but also promote the growth of beneficial gut bacteria and increase the production of short-chain fatty acids (SCFAs), suggesting dual health benefits [15]. Group 4: Implications for Supplementation - The findings suggest that NR and NMN are superior choices for NAD+ supplementation, emphasizing the need for long-term use to achieve stable effects [15]. - The study underscores the importance of gut microbiota in nutrient metabolism and suggests that personalized supplementation strategies for specific populations, such as the elderly or those with gut dysbiosis, warrant further exploration [15].

Core Viewpoint - The study reveals a new mechanism by which lactate in the tumor microenvironment inhibits the anti-tumor function of natural killer (NK) cells through lactylation modification, providing new intervention targets and strategies to enhance NK cell cytotoxicity [1][3]. Group 1 - The research indicates that elevated levels of lysine lactylation (Kla) in NK cells are associated with impaired NAD metabolism, mitochondrial fragmentation, and reduced cytotoxicity [3]. - Supplementation with nicotinamide riboside (NR) and honokiol, a SIRT3 activator, enhances NK cell cytotoxicity by lowering intracellular Kla levels [3]. - The combination of NR and honokiol regulates Kla's effect on the protein kinase ROCK1, inhibiting the ROCK1-DRP1 signaling pathway to prevent mitochondrial fragmentation and restore NK cell activity against leukemia both in vivo and in vitro [3]. Group 2 - The study emphasizes that lactate-induced lactylation represents a new target for immunotherapy based on NK cells, aiming to enhance their tolerance to lactate within the tumor microenvironment [5]. - The research was conducted by a collaborative team from the University of Science and Technology of China and Fudan University, with key contributors including researchers Jin Jing, Yan Peidong, and Wang Dongyao [5].