NAD+ is linked to sleep because it is part of the body clock itself. NAD+ levels rise and fall over 24 hours, and the enzyme SIRT1 uses NAD+ to keep clock genes in time. Laboratory research shows this loop weakens with age, but human evidence is limited: one small trial reported less daytime drowsiness, and there are no trials on jet lag.
This article is for adults who sleep less well than they used to, or who travel across time zones, and want to know whether NAD+ has a role. It explains how NAD+ and the circadian clock are connected, what the human studies do and do not show, when to time a dose so it does not disturb your night, and how to keep a protocol going on a long trip.
Educational content, not medical advice. NAD+ is not intended to diagnose, treat, cure or prevent any disease. Speak to a licensed prescriber before starting any injectable protocol, especially if you are pregnant or breastfeeding, have active or historic cancer, or take regular medication. Ongoing insomnia, loud snoring or waking unrefreshed should be checked by a doctor.
How NAD+ connects to the body clock
Almost every cell runs its own 24-hour clock. A set of genes, led by CLOCK and BMAL1, switches on a second set, PER and CRY, whose proteins build up during the day and then shut their own production down. The cycle takes roughly a day to complete, and a master clock in the brain, the suprachiasmatic nucleus, keeps all the cellular clocks aligned using light as its main cue.
NAD+ is woven into that loop. In 2009 two research groups, publishing side by side in Science, showed that CLOCK and BMAL1 control the gene for NAMPT, the enzyme that recycles NAD+. The result is that NAD+ levels themselves rise and fall on a daily rhythm. That rhythm then feeds back into the clock through SIRT1, a sirtuin enzyme that needs NAD+ to work. SIRT1 adjusts CLOCK, BMAL1 and PER2, which helps the cycle stay precise. Earlier work in Cell, in 2008, had shown that cells lacking SIRT1 activity keep a noticeably disrupted rhythm.
Put simply: the clock sets the NAD+ rhythm, and the NAD+ rhythm helps keep the clock in time. Our explainer What is NAD+ covers the sirtuins and their other roles.
Why the link matters as we get older
Sleep changes with age. Most people find they fall asleep and wake earlier, spend less time in deep sleep and wake more often in the night. Some of this is normal and some is driven by health, medication and lifestyle. The question researchers have asked is whether falling NAD+ plays a part.
Human tissue studies show NAD+ declining through adult life; a 2012 study in PLoS ONE measured levels in older adults at roughly half those of younger adults. In mice, the picture goes further. A 2013 study in Cell found that SIRT1 activity in the brain's master clock falls with age, and that older mice with more SIRT1 kept a stronger daily rhythm. A 2020 study in Molecular Cell found that boosting NAD+ in older mice with a precursor restored part of the youthful pattern of clock gene activity.
Those are animal results. They make the connection plausible. They do not show that raising NAD+ improves sleep in people.
What the human studies show
Very few human trials have measured sleep directly. The table sets out what exists and how much weight it can bear.
| Study | Who and what | Sleep or clock finding |
|---|---|---|
| Kim et al., 2022 | About 100 adults aged 65 and over in Japan; NMN 250mg a day or placebo for 12 weeks, taken in the morning or the afternoon | Afternoon NMN intake was associated with less daytime drowsiness and better leg function. Small, short and with modest effects; it did not test injected NAD+. |
| Martens et al., 2018 | 30 healthy adults aged 55 to 79; NR 1000mg a day for 6 weeks | Blood NAD+ rose by about 60%. Sleep was not a measured outcome. |
| Mouse studies, 2013 and 2020 | Older mice with raised SIRT1 or NAD+ | Stronger daily rhythms and partly restored clock gene activity. Not directly applicable to people. |
| Jet lag trials | None published for NAD+, NMN or NR | No evidence either way. |
The honest summary is that the mechanism is well established in the laboratory, one small human trial hints at a daytime alertness effect that may depend on timing, and nothing yet shows that NAD+ helps people fall asleep, stay asleep or adjust to a new time zone faster. Some customers tell us they sleep more deeply in the first weeks of a protocol, and others notice no change. Both are anecdote.
What NAD+ is not
- Not a sleeping aid. NAD+ has no sedative effect and does not act on the brain's sleep signals the way melatonin or sleeping tablets do.
- Not a treatment for insomnia. Long-term insomnia has effective treatments, including cognitive behavioural therapy for insomnia, which NICE guidance recommends as the first option. NAD+ is not a substitute.
- Not a jet lag cure. The clock resets mainly through light, meal timing and activity. NAD+ cannot override those cues.
The research on NAD+ for energy and fatigue follows the same pattern: solid biology, modest and mixed human results, and no stimulant or sedative effect.
When to inject NAD+ so it does not disturb sleep
Timing is the most practical thing to get right. NAD+ supports daytime energy metabolism, and a small number of people find that a dose late in the evening makes it harder to wind down. The natural NAD+ rhythm is also tied to the active part of the day. For both reasons, most people inject in the morning or around midday.
- Usual time: morning, after a light breakfast. Food first also reduces the chance of mild nausea.
- If mornings do not suit you: early afternoon is fine. The Kim study above suggests later in the day is not a problem for daytime alertness.
- Avoid: the last three or four hours before bed, until you know how you respond.
- Be consistent: injecting at roughly the same time on dose days makes it easier to spot any effect, good or bad.
The dose itself does not change for sleep. The usual protocol is 50mg per injection (0.3ml, 30 clicks on the pen), once a day for the first three days and then every other day. Our dosage guide explains the gentler 25mg start and the upper limits, and the dosage calculator converts any dose into pen clicks or syringe units.
A practical plan for jet lag
Because there is no evidence that NAD+ speeds up adjustment to a new time zone, the plan below is built around what does work, with NAD+ simply kept on schedule so the trip does not break your routine.
| When | What to do | Where NAD+ fits |
|---|---|---|
| 2 to 3 days before | Shift bedtime 30 to 60 minutes towards the destination time zone | Keep your usual dose days; no need to add extra doses |
| Travel day | Drink water, go easy on alcohol, sleep on the plane only if it is night at your destination | Skip the dose if the day is chaotic, or take it before you leave home |
| First days on arrival | Get outdoor daylight in the morning local time when flying east, and in the afternoon and evening when flying west; eat meals on local time | Inject in the local morning on your next dose day |
| Back home | Repeat the light and meal timing in reverse | Return to your usual dose days; do not double up for missed doses |
Missing one or two doses over a trip makes little difference. What matters over a month is overall consistency, not any single day.
Travelling with your NAD+ pen
Cartridges and vials should be kept in the fridge, between 2 and 8 °C and away from light, and should not be frozen. For travel:
- Pack the pen, cartridge and needles in your hand luggage, not the hold, where temperatures can drop close to freezing.
- Use an insulated pouch with a cool pack that is not in direct contact with the cartridge, and put everything back in a fridge as soon as you arrive.
- Bring enough needles for the trip and a small sharps container, or the one from your kit, for used needles.
- Airline and border rules for injectable products and needles differ. Check with your airline before you fly, and carry the product in its original packaging. A note from your prescriber can help at security.
The complete UK guide to NAD+ injections covers storage, safety and who should not use NAD+.
Sleep problems that need a doctor first
Before looking at NAD+ for poor sleep, it is worth ruling out the common causes that have specific treatments:
- Sleep apnoea, especially with loud snoring, pauses in breathing or waking unrefreshed after a full night.
- Restless legs, which is sometimes linked to low iron.
- Anxiety, low mood or prolonged stress.
- Menopause symptoms such as night sweats.
- Side effects of regular medication, alcohol or late caffeine.
If poor sleep has lasted more than a few weeks or affects how you function during the day, see your GP. NAD+ is a reasonable thing to explore once those have been checked, as part of a routine that already includes regular sleep and wake times, daylight and less alcohol.
Which kit to start with
- Want to see how you respond first: the NAD+ Trial Kit includes the pen and one 500mg cartridge, ten doses or about two weeks.
- Want a fair test over a full month, or have a trip coming up: the NAD+ Discovery Kit includes the pen and two 500mg cartridges, roughly five weeks at the usual rhythm, so a holiday does not interrupt the protocol.
Both are pre-mixed and third-party verified at 99.5% purity. Delivery is free across the UK, and subscriptions can be paused or cancelled at any time, which is useful around travel. The full range is in the NAD+ collection.
Frequently asked questions
Does NAD+ help you sleep?
It has not been shown to. NAD+ is part of the body clock, and animal research links falling NAD+ to weaker daily rhythms, but no human trial has shown that NAD+ helps people fall or stay asleep. One small trial of NMN reported less daytime drowsiness.
Can NAD+ keep you awake at night?
Some people find a dose late in the evening makes it harder to wind down. NAD+ is not a stimulant, but it supports daytime energy metabolism, so most people inject in the morning or early afternoon.
What is the best time of day to inject NAD+?
Morning after a light breakfast suits most people, and early afternoon is a good alternative. Avoid the last three or four hours before bed until you know how you respond, and keep the time roughly the same on each dose day.
Does NAD+ help with jet lag?
There is no published trial of NAD+, NMN or NR for jet lag. The body clock resets mainly through light, meal timing and activity. Keeping your NAD+ protocol on schedule during a trip is sensible, but it is not a jet lag treatment.
Can I take NAD+ on a plane?
Pack the pen, cartridge and needles in hand luggage, in an insulated pouch with a cool pack, and refrigerate them on arrival. Rules on injectables and needles vary, so check with your airline and carry the product in its original packaging.
Can I take NAD+ with melatonin?
There is no known interaction, but there are no studies of the combination either. Melatonin is a prescription medicine in the UK, so ask the prescriber who supplied it before combining the two.
Sources
- Nakahata Y et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell, 2008.
- Asher G et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell, 2008.
- Nakahata Y et al. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science, 2009.
- Ramsey KM et al. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science, 2009.
- Chang HC, Guarente L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell, 2013.
- Levine DC et al. NAD+ controls circadian reprogramming through PER2 nuclear translocation to counter aging. Molecular Cell, 2020.
- Massudi H et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS ONE, 2012.
- Martens CR et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 2018.
- Kim M et al. Effect of 12-week intake of nicotinamide mononucleotide on sleep quality, fatigue, and physical performance in older Japanese adults: a randomized, double-blind placebo-controlled study. Nutrients, 2022.
