Charles Brenner is a researcher working in the fields of biochemistry and cellular metabolism. His research focuses on NAD+ homeostasis, metabolic regulation, and the physiological effects of nicotinamide riboside supplementation in conditions such as mild cognitive impairment, long-COVID, and cancer survivorship. He also investigates metabolic signaling nodes in cancer, liver disease, and genetic metabolic disorders.
In a crossover trial evaluating nicotinamide riboside in older men, the anti-inflammatory effect exhibited a carryover that persisted for three weeks into the subsequent placebo period.
"In fact, it was so strong that the people that had the NR first followed by placebo still had lower anti-inflammatory results after three weeks on placebo." (said at 0:20:04)
In a randomized, double-blind, crossover study of 12 older men receiving 1 g/day of nicotinamide riboside (NR) or placebo for 21 days (PMID 31412242), NR supplementation depressed circulating levels of inflammatory cytokines (such as IL-6, IL-5, IL-2, and TNF-alpha). An observed carryover effect occurred in the group receiving NR first followed by placebo, with inflammatory cytokines remaining suppressed during the subsequent period. The speaker's phrasing ('lower anti-inflammatory results') is slightly confused in terminology (meaning lower pro-inflammatory cytokines / reduced inflammation), but accurately reflects the findings of a persistent anti-inflammatory carryover effect in this small trial.
Resveratrol and pterostilbene do not increase the activity of the SIRT1 enzyme.
"pterostilbene and resveratrol don't actually increase the activity of SIRT1 anyway" (said at 1:22:12)
Biochemical investigations confirmed that resveratrol (and related polyphenols like pterostilbene) does not directly enhance the catalytic activity of the SIRT1 enzyme when tested with native, unmodified substrates (such as p53 or PGC-1alpha). The initial reports of direct SIRT1 activation were demonstrated to be an artifact of the artificial fluorophore (Fluor de Lys) attached to the peptide substrate in commercial screening assays. However, in intact cells and in vivo models, resveratrol can increase SIRT1 signaling indirectly through upstream pathways, such as activation of AMPK.
- supports: Resveratrol is not a direct activator of SIRT1 enzyme activity. (Chemical biology & drug design 2009) · cited 424x in the literature
"resveratrol does not activate SIRT1 in vitro in the presence of either a p53-derived peptide substrate or acetylated PGC-1alpha isolated from cells, and (iii) although SIRT1 deacetylates PGC-1alpha in both in vitro and cell-based assays, resveratrol did not activate SIRT1 under these conditions. Based on these observations, we conclude that the pharmacological effects of resveratrol in various models are unlikely to be mediated by a direct enhancement of the catalytic activity of the SIRT1 enzyme." (abstract, results, passage verified)
pubmedfull study (doi) - supports: SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. (The Journal of biological chemistry 2010) · cited 908x in the literature
"SRT1720, its structurally related compounds SRT2183 and SRT1460, and resveratrol do not lead to apparent activation of SIRT1 with native peptide or full-length protein substrates, whereas they do activate SIRT1 with peptide substrate containing a covalently attached fluorophore... Taken together, we conclude that SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1." (abstract, results, passage verified)
pubmedfull study (doi)