Nicotinamide Riboside + Pterostilbene (Basis): The Combination NAD Product Trial Legacy
"Basis" is the trade name of the first major commercial NAD precursor combination — 250 mg of nicotinamide riboside (NR) plus 50 mg of pterostilbene per day — launched by Elysium Health in 2014 under unusual academic-industry circumstances (founder Leonard Guarente at MIT, a roster of Nobel laureate scientific advisors). The product anchored the consumer NAD-supplementation market and generated the first formal clinical trials of NR + pterostilbene combination dosing in humans. The trial record is informative, modest, and clarifying.
The mechanistic rationale
NR is a small-molecule precursor that is converted intracellularly to NAD+ via the NRK kinases. Pterostilbene is a methylated analogue of resveratrol with longer half-life and higher oral bioavailability; in cell models, it activates sirtuin-1 (SIRT1), the NAD-dependent deacetylase central to many longevity hypotheses. The proposed synergy: NR supplies the cofactor, pterostilbene stimulates the consuming enzyme [1]. Whether this actually plays out at the doses used has been the empirical question.
The first human trial
The 2017 pivotal trial randomised 120 adults aged 60–80 to NR + pterostilbene at 250 mg / 50 mg, 500 mg / 100 mg, or placebo, daily for 8 weeks. Whole-blood NAD+ rose 40% at the low dose and 90% at the high dose, with sustained elevation through follow-up. No statistically significant changes in clinical endpoints (blood pressure, walking distance, oxidative stress markers) were seen, except a small drop in systolic blood pressure in stage-1 hypertensive participants [2]. This is the trial that established that NR is bioavailable and reliably raises blood NAD+ at consumer doses.
The follow-on trials
Subsequent randomised trials have replicated the NAD+ elevation finding and added small physiological signals: improved aortic stiffness (carotid–femoral pulse wave velocity) in middle-aged adults, modest improvement in mitochondrial function biomarkers in older muscle, and small reductions in inflammatory cytokines [3]. Trial sizes are small (n=30–70) and most are short (8–12 weeks). No trial has demonstrated improvement in a hard endpoint — cognition (clinically meaningful), incident frailty, cardiovascular events, or mortality.
What the data establish, and what they do not
Established: oral NR raises blood NAD+ reproducibly; the combination with pterostilbene is well tolerated; mild improvements in vascular and inflammatory biomarkers occur in some trials. Not established: whether the NAD+ elevation produces clinically meaningful effects on aging, neurodegeneration, or longevity. The biomarker–clinical-endpoint gap is the central unanswered question for the entire NAD-precursor field, including NMN, NR, and combination products [4].
Safety and the NR controversy
NR has been well tolerated across multiple trials at doses up to 1,000 mg/day; the most common adverse events are mild GI symptoms. There is no signal of harm. A 2024 pre-clinical paper suggested that high-dose NR might accelerate certain tumour models, which generated debate but has not been replicated and is not currently considered a clinical concern at consumer doses [5]. Pterostilbene at 100 mg/day has a small literature on LDL lowering but a less reassuring safety profile at very high doses than NR.
The product-versus-evidence picture
Basis was the first NAD combination product with clinical trial backing, but the trials it sponsored have not produced evidence of clinical benefit beyond biomarker elevation. The commercial NAD market has expanded substantially to include NMN, IV NAD, and a variety of combinations, almost none of which have trial data approaching the rigour of Basis. The history of Basis is partly the history of the NAD field figuring out what its hypothesis actually predicts — and learning that raising a biomarker is not the same as slowing biological aging.
Practical position
NR + pterostilbene combinations are well tolerated and produce reliable NAD+ elevation. The clinical benefit at consumer doses is modest at best and unproven for any hard endpoint. For a healthy adult interested in the NAD hypothesis, an empirical trial is low-risk; expectations should be calibrated to the trial data, not the marketing. For someone with mitochondrial disease, sarcopenia, or specific neurodegenerative conditions, ongoing clinical trials are the more appropriate venue.
Sources
- Trammell SA, Schmidt MS, Weidemann BJ, et al. "Nicotinamide riboside is uniquely and orally bioavailable in mice and humans." Nat Commun, 2016;7:12948. PMID: 27721479. DOI: 10.1038/ncomms12948.
- Dellinger RW, Santos SR, Morris M, et al. "Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study." NPJ Aging Mech Dis, 2017;3:17. PMID: 29184669. DOI: 10.1038/s41514-017-0016-9.
- Martens CR, Denman BA, Mazzo MR, et al. "Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults." Nat Commun, 2018;9(1):1286. PMID: 29599478. DOI: 10.1038/s41467-018-03421-7.
- Rajman L, Chwalek K, Sinclair DA. "Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence." Cell Metab, 2018;27(3):529-547. PMID: 29514064. DOI: 10.1016/j.cmet.2018.02.011.
- NIH National Institute on Aging. "Geroscience Research: NAD Precursors." Updated 2024.