What is Nicotinamide Riboside?
Nicotinamide riboside (NR) is a naturally occurring form of vitamin B-3 present in very small amounts in the human diet, found in milk, yeast, and beef. NR acts as a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a vital coenzyme or helper molecule that plays a key role in ATP production, the energy currency that fuels cellular activities (1).
NAD+ is also key for the function of sirtuins, enzymes involved in aging that regulate gene expression and DNA repair (2) (a more in-depth article into the NAD+ biology is coming soon, stay tuned!).
Levels of NAD+ naturally decline as we age. NAD+ depletion plays a key role in the ageing of human cells by limiting energy production and DNA repair (3) as well as age-related diseases, including metabolic disorders, cancer, and neurodegenerative diseases (4).

NR supplementation: Boosting low NAD+ levels to tackle aging
NR has become one of the most studied NAD+ precursor as numerous animal and human studies have reported a variety of health benefits of NR-mediated elevated NAD+ levels in the body (5-17). NR supplementation has elicited health benefits in both healthy and diseased humans, for the treatment of a number of cardiovascular, neurodegenerative, autoimmune and metabolic disorders.
Given that the presence and morbidity of such conditions has increased over the last decades in modern societies due to poor lifestyle habits that reduce NAD+ levels, such as altered circadian rhythms, chronic stress or sedentarism (17, 18), there is an increased interest in replenishing NAD+ levels in the body through supplementation to support health span and longevity.
The Benefits of using NR as a supplement
Nicotinamide Riboside: The Next-Generation NAD+ Precursor with a Promising Future
Nicotinamide riboside (NR) is a naturally occurring compound that has been shown to have a number of positive effects on human health. Here are some of the key findings from recent studies:
Cardiovascular health: NR has been shown to improve vascular endothelial function, which is important for maintaining healthy blood pressure and circulation. (11)
Muscles and metabolism: NR has been reported to can help to increase muscle mass and improve metabolic rate, even during sleep. It also has anti-inflammatory effects, which can improve exercise performance and endurance, as well as overall healt, reducing the risk of developing autoimmune conditions. (12, 13, 14)
Mitochondria and gut health: NR can improve mitochondrial function and promote stem cell differentiation in muscles. It can also increase the diversity of the gut microbiota, which is important to maintain a healthy gastrointestinal system and mental health, as well as for overall health and well-being. (15)
Brain health: NR has potential neuroprotective effects, which may help to protect the brain from age-related decline and disease. (16)
Infectious diseases: NR may also support the treatment of infections, including COVID-19. (17)

Evidence of NR supplementation in human clinical trials
The following mentioned studies are a summary of the most recent human clinical trials published in high-impact factor international scientific journals:
Initiation of Clinical Trials for Nicotinamide Riboside (NR)
In 2016, clinical trials began investigating the bioavailability of nicotinamide riboside (NR) in humans. A study administered three doses of NR (100 mg, 300 mg, and 1,000 mg) to participants, with a 7-day washout period between doses.
Results showed that NR was bioavailable in supplement form and increased NAD+ levels in a dose-dependent manner, with higher doses leading to greater NAD+ increases. (22)
Reinforcing Bioavailability and Safety
In 2017, two additional studies confirmed NR's effectiveness in raising NAD+ levels. In the first, participants received daily doses of NR combined with pterostilbene (PT), a polyphenol found in blueberries with anti-aging properties, over eight weeks. The lower dose resulted in a 40% increase in NAD+, while a higher dose nearly doubled NAD+ levels. (23)
The second study involved increasing doses of NR over eight days, starting with 250 mg and escalating to 2,000 mg. By day nine, NAD+ levels had risen by 35% to 168% across participants.
Limited Effects on Metabolic Health
A 2018 study examined the effects of NR supplementation over a 12-week period, showing that NR supplementation raised NAD+ levels by ~60%. The study also tested for chronic NR supplementation, showing it is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults. In addition, the effects of NR supplementation on physiological function suggested the ability of NR to reduce blood pressure and aortic stiffness, two clinically important risk indicators of cardiovascular function and health. However, its effects and others tested such as physical activity, and glucose regulation were not significant, and mentioned that a larger clinical trial will confirm these results.
In terms of side effects, only 2 out of the 30 enrolled subjects (<10%) dropped out of the study due to a complaint of side effects, both occurring while subjects were in the placebo phase (headache and skin rash); no subject dropped out during the NR treatment condition. Additionally, another study the same year found no improvement in insulin sensitivity or glucose metabolism in participants who received 2,000 mg of NR daily for 12 weeks. (24)
Promising Findings in ALS and Skeletal Muscle Research
In 2019, researchers explored NR's potential in slowing the progression of amyotrophic lateral sclerosis (ALS) and improving associated health outcomes. Over four months, participants receiving NR showed improvements in ALS symptoms, muscular strength, and pulmonary function.
Another study on older adults showed that daily NR supplementation increased NAD+ levels in skeletal muscle and exhibited anti-inflammatory properties. (25)
Safety of High-Dose Nicotinamide Riboside in Parkinson's Disease
A 2023 phase I trial assessed the safety and tolerability of high-dose nicotinamide riboside (NR) in individuals with Parkinson’s disease (PD). In this randomized, double-blind study, 20 participants received either 1,500 mg of NR twice daily or a placebo for four weeks. The primary focus was safety, while secondary outcomes included NAD+ level changes and PD symptom severity. (15)
The study found no moderate or severe adverse events, and NR was well tolerated. Participants on NR experienced a significant fivefold increase in blood NAD+ levels, and mild improvement in PD symptoms was observed, though linked to levodopa timing rather than solely to NR. These results support further trials with NR doses up to 3,000 mg per day, with continued safety monitoring. This trial adds to the growing body of evidence supporting NR's potential for neurodegenerative diseases, particularly by raising NAD+ levels safely.
Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study
In a recent study (2023), researchers investigated the impact of long-term nicotinamide riboside (NR) supplementation on mitochondrial function and metabolic health in humans. (14) Over five months, 20 pairs of body mass index (BMI)-discordant monozygotic twins (males and females aged 40 on average, >18 years) were given escalating doses of NR (250 to 1000 mg/day). NR enhanced systemic NAD+ metabolism, increased muscle mitochondrial numbers, improved myoblast differentiation, and positively influenced gut microbiota composition in both twins.
Additionally, NR appeared to affect epigenetic regulation of gene expression in muscle and adipose tissue. Despite these improvements, NR did not significantly alter adiposity or metabolic health. The findings indicate that NR effectively modifies NAD+ metabolism, resulting in improved muscle mitochondrial biogenesis and stem cell function – indicating health benefits in physical performance, recovery, muscle growth and repair –, gut microbiota – indicating health benefits in overall metabolic and digestive health – in humans, irrespective of BMI.
Overall, though detailed mechanistic effects on metabolic function remain inconclusive and larger clinical trials are needed to fully uncover the potential benefits of these supplements, the existing human clinical trials have highlighted NR's capacity to raise NAD+ levels and demonstrate a variety of health benefits, which promote a more balanced and resilient body, in both healthy and diseased humans.
Does Nicotinamide Riboside have any Risks or secondary effects? Effective, Convenient and Safe
Nicotinamide riboside chloride is a stable and safe form of nicotinamide riboside. It does not require refrigeration and can be stored at room temperature, making it convenient to take. Customers only need to comply with the standard guidelines that apply to all food supplements: keep away the supplement from direct sunlight, extreme heat, and humidity and store the capsules inside the bottle with the lid closed.
Different studies have concluded that long-term supplementation in humans is well-tolerated and shows no serious adverse effects with doses up to 2g/day. (7, 8, 18, 19).
Nicotinamide Riboside has high oral bioavailability (20), which means that it is well-absorbed by the body after ingestion. This is important because it ensures that a significant amount of the NR that you consume is actually available to your cells.
The Key Takeaway
Nicotinamide riboside (NR) is a safe and effective way to boost NAD+ levels, which is a key factor in anti-aging. NAD+ levels decline naturally with age, and this decline is linked to a number of age-related diseases.
By boosting NAD+ levels, NR can help to slow down or even reverse some of the effects of aging. For example, NR has been shown to improve muscle function, metabolism, mitochondrial function, gut health, and brain health.
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