Get Your Personalized Supplement StackSupplement Stack Quiz

Niagen Nicotinamide Riboside

Also known as: NR, Niagen, Nicotinamide Riboside

Overview

Nicotinamide Riboside (NR) is a naturally occurring form of vitamin B3 and a direct precursor to nicotinamide adenine dinucleotide (NAD+), a vital coenzyme involved in numerous cellular metabolic processes. Found in trace amounts in milk and other foods, NR supplementation aims to elevate NAD+ levels within the body. This elevation is believed to support mitochondrial function, enhance cellular energy metabolism, and potentially contribute to healthy aging by mitigating age-related cellular decline. NR is orally bioavailable, meaning it is well-absorbed when taken by mouth, and has been shown to dose-dependently increase NAD+ and related metabolites in the bloodstream. It is generally well-tolerated, with research indicating its safety and efficacy in boosting NAD+ levels, though long-term clinical outcome data are still being gathered.

Benefits

Oral NR supplementation robustly increases whole blood NAD+ levels in a dose-dependent manner, with increases of approximately 22% at 100 mg, 51% at 300 mg, and 142% at 1000 mg doses within two weeks, sustained over eight weeks. This effect is well-supported by randomized controlled trials (RCTs) [1]. Some studies suggest NR may have anti-inflammatory potential, with reported reductions (approximately 50-70%) in plasma inflammatory markers like IL-6, IL-5, and IL-2 in older adults [2]. Furthermore, research indicates NR may improve brain NAD+ levels and reduce inflammatory cytokines in neurodegenerative conditions such as Parkinson’s disease, suggesting potential neuroprotective effects [3]. While NAD+ increases are consistently observed and statistically significant, functional outcomes like improvements in muscle strength or mitochondrial bioenergetics have shown mixed or no significant changes in smaller trials [2]. The primary benefit observed is the consistent and significant elevation of NAD+ levels, which is foundational for various cellular processes.

How it works

Nicotinamide Riboside (NR) functions primarily by serving as a direct precursor to nicotinamide adenine dinucleotide (NAD+). Once ingested, NR is converted intracellularly into NAD+ through the salvage pathway, a crucial metabolic route for NAD+ biosynthesis. This process enhances cellular energy metabolism and supports optimal mitochondrial function, as NAD+ is a key coenzyme in the electron transport chain. By increasing systemic NAD+ pools, NR can modulate inflammatory cytokines and influence gene expression through epigenetic mechanisms, particularly those linked to NAD+-dependent enzymes like sirtuins and PARPs. These enzymes play roles in DNA repair, cellular stress response, and metabolism. NR is orally bioavailable, with studies confirming dose-dependent increases in NAD+ metabolites in both blood and tissues.

Side effects

Nicotinamide Riboside (NR) is generally considered safe and well-tolerated, with studies reporting no serious adverse events when taken at doses up to 1000 mg/day for eight weeks [1, 3]. Unlike nicotinic acid, another form of vitamin B3, NR does not cause the common 'flushing' sensation. There are no common side effects reported at a significant frequency (above 5%). Uncommon side effects (1-5%) or rare side effects (less than 1%) have not been documented in clinical trials. Currently, no significant drug interactions have been reported, though research in this area is limited. There are no clearly established contraindications for NR supplementation. Safety data primarily come from studies involving overweight but otherwise healthy adults and older men, suggesting that more research is needed to fully assess its safety in diverse populations, including pregnant or breastfeeding women and individuals with pre-existing medical conditions.

Dosage

The minimum effective dose of Nicotinamide Riboside (NR) to increase NAD+ levels is 100 mg/day, which has been shown to increase whole blood NAD+ by approximately 22% [1]. Optimal dosage ranges typically fall between 300 mg/day and 1000 mg/day, as these doses lead to greater NAD+ elevation. A dose of 1000 mg/day has been demonstrated to be well-tolerated [1]. The maximum safe dose established in short-term studies is up to 1000 mg/day for eight weeks; however, longer-term upper limits have not been fully determined. Daily dosing is recommended to maintain elevated NAD+ levels. NR chloride, often branded as Niagen, is the common supplement form. Oral bioavailability is confirmed, and no specific cofactors are identified as necessary to enhance its absorption or efficacy.

FAQs

Does NR cause flushing?

No, Nicotinamide Riboside (NR) does not typically cause the flushing sensation associated with nicotinic acid, another form of vitamin B3.

How quickly does NR raise NAD+?

Studies indicate that Nicotinamide Riboside (NR) can significantly raise NAD+ levels in the blood within two weeks of consistent supplementation.

Is NR effective for muscle strength or metabolism?

Evidence is mixed; some studies have not shown significant improvements in mitochondrial bioenergetics or muscle strength after short-term NR supplementation.

Is NR safe long-term?

Short-term safety of NR up to 1000 mg/day for eight weeks is established, but long-term safety data are currently limited.

Does NR reduce inflammation?

Some evidence suggests that NR may reduce certain inflammatory cytokines, particularly in older adults, indicating potential anti-inflammatory effects.

Research Sources

https://www.nature.com/articles/s41598-019-46120-z – This randomized, double-blind, placebo-controlled trial involving overweight adults demonstrated that Nicotinamide Riboside (NR) supplementation dose-dependently increased whole blood NAD+ levels (22%-142%) at doses ranging from 100 mg to 1000 mg/day over 8 weeks. The study reported no significant adverse events or flushing, supporting NR's safety and efficacy in boosting NAD+.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10692436/ – This crossover RCT in 12 older men found that 500 mg of NR twice daily increased skeletal muscle NAD+ metabolites but not NAD+ itself. It did not show improvements in mitochondrial bioenergetics or muscle strength, but observed significant reductions in inflammatory cytokines, suggesting anti-inflammatory effects despite limited functional improvements.
https://journals.physiology.org/doi/pdf/10.1152/ajpendo.00242.2023 – This systematic review, guided by PRISMA, synthesized clinical trials on NR, confirming its safety up to 1000 mg/day and its ability to increase NAD+ in blood and brain. It highlighted NR's potential neuroprotective effects, particularly through inflammation reduction in Parkinson’s disease, emphasizing its good tolerability and emerging therapeutic potential.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7352172/ – This review summarizes the metabolic benefits, safety profile, and bioavailability of Nicotinamide Riboside (NR). It supports the translation of NR into therapeutic use for metabolic and age-related diseases, providing a comprehensive overview of its properties and potential applications.