NADream: Effects of Nicotinamide Adenine Dinucleotide Supplementation on Sleep Quality in Healthy Individuals

Nicotinamide adenine dinucleotide (NAD+) is important for regulating cellular energy metabolism, mitochondrial function, and circadian rhythms, which are key processes involved in the sleep-wake cycle and sleep regulation. Nicotinamide riboside (NR) supplementation has been shown to elevate NAD+ levels in humans. Higher NAD+ levels may support better sleep by restoration of mitochondrial efficiency and reducing oxidative stress.

As people age, there is evidence of a decline in NAD+ levels, which may lead to mitochondrial dysfunction, oxidative stress, and disruptions in circadian rhythms. These changes can negatively affect sleep architecture and reduce sleep quality. Impaired NAD+ metabolism has been linked to problems with the molecular clock, which regulates circadian timing through effects on sirtuin activity and clock genes such as BMAL1. NAD+ also supports brain metabolism by maintaining mitochondrial function, promoting neuroprotection, regulating redox balance, and reducing neuroinflammation. By restoring NAD+ levels, NR supplementation may help improve mitochondrial efficiency, decrease oxidative damage, and enhance sleep-related cellular maintenance. NR may also support synchronization of circadian rhythms, further promoting healthy sleep. Its effects also include modulating neuroinflammatory pathways and strengthening cellular resilience against oxidative stress, both of which are essential for maintaining cognitive functions and neural plasticity during sleep.

The NADream study will test whether NR supplementation can improve both objective and subjective measures of sleep in healthy adults. Sleep will be assessed using polysomnography (PSG), the gold standard for objective sleep measurement, along with actigraphy, Somnofy sleep monitoring, and the Pittsburgh Sleep Quality Index (PSQI). This study will be a randomized, placebo-controlled, double-blind, parallel-group design. Participants will be randomly assigned to receive ether NR or a placebo for 8 weeks. The findings from this study will help determine whether NR supplementation could be a viable therapeutic option to explore further in this area.

Inclusion criteria

• Participant must be 40 to 60 years of age inclusive, at the time of signing the informed consent.
• Male or female.
• Participants who are healthy as determined by medical evaluation including medical history and physical examination.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the study protocol.
• Self-reported normal sleep patterns, assessed by Pittsburgh sleep quality index (PSQI; cutoff ≤ 5).
• No current use of sleep medications or supplements.
• Able to wear polysomnographic equipment and actigraphy during nighttime.

Exclusion criteria

• History of sleep disorders (e.g. insomnia, sleep apnea).
• Abnormal findings on PSG, such as sleep related breathing disorders (apnea-hypopnea index (AHI) ≥ 5), sleep related movement disorders (periodic limb movement index (PLMI) ≥ 15, and parasomnias (like REM sleep behavior disorder (RBD)).
• Chronic use of alcohol, tobacco, or medications affecting sleep.
• Significant psychiatric or medical conditions (including neurological, heart, lung, or sleep disorders/diseases).
• Travelled >1 time zone and night work <1 month before study, or during the study.
• Extreme chronotype according to the Composite Morningness Questionnaire (evening type; <22 and morning type >44).
• Pregnancy.
• Breastfeeding.
• Supplements resulting in > 20 mg daily of nicotinamide riboside, nicotinamide mononucleotide (NMN), niacin (vitamin B3, nicotinic acid amide or other vitamin B3 analogues) less than 3 months prior to randomization.
• Participation in other clinical trials last 3 months.
• Deemed ineligible by lead principal investigator.