The reading shelf

Human outcomes

The NMN walking-distance trial is the most direct connection here with physical performance: healthy middle-aged adults, a placebo comparison and 60 days of observation. The muscle insulin-sensitivity trial asks a more specific metabolic question in prediabetic, postmenopausal women over 10 weeks.

My suggested starting pair is those experiments, followed by the review of human NAD+ precursor supplementation during ageing. Its account of limited efficacy and sparse tissue-specific data provides useful resistance to enthusiasm generated by an individual result.

Samples and tissues

The muscle-biopsy study in older men connects sarcopenia with low NAD+ and impaired mitochondrial biology. The NAD metabolome methods paper validates an analytical method in mouse plasma, whole blood and liver. NAD+ production, cycling and compartmentalisation supply the broader biochemical context.

Cellular roles and consumption

NAD+ in ageing, metabolism and neurodegeneration gives a compact account of the molecule's redox and signalling roles. The review of cellular processes during ageing follows the enzymes that consume NAD+. The CD38 mouse experiment tests one of those consumers genetically.

NAMPT in resistant melanoma cell lines and mouse xenografts makes biological context unavoidable: the experiment investigated inhibiting NAD+ synthesis in tumour models. It supplies a caution about universal biological goals, without establishing a human supplementation risk.

Routes and movement in experimental models

ANT1-deficient mice given nicotinamide riboside provide a specific model of exercise intolerance and metabolic restoration. Precursor cycling between mice and their gut microbiome reveals a surprisingly indirect route to host NAD+. The older human fibroblast culture experiment follows extracellular NAD breakdown and cellular uptake of a hydrolysis product. I especially like these route papers for the complications they introduce into a straight-line replenishment story.