NAD+ is linked to energy because mitochondria need it to turn food into ATP, and levels fall with age. Human trials show that raising NAD+ is safe and lifts blood levels, but results on how energetic people actually feel are mixed: some small studies report better endurance, others find no change. It supports energy production rather than acting as a stimulant.
This article is for adults who feel flatter than they used to and are wondering whether NAD+ has anything to do with it. It explains the biology, sets out what the human trials found and did not find, and covers the causes of tiredness that NAD+ will not touch and that deserve a GP appointment first.
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. Persistent fatigue has many medical causes and should be checked by a doctor.
How NAD+ connects to cellular energy
Almost all the energy your body uses is made inside mitochondria, the small structures in each cell that burn glucose and fat to produce ATP. NAD+ sits at the centre of that process. During glycolysis and the citric acid cycle it collects electrons from the fuel and becomes NADH. NADH then hands those electrons to the electron transport chain, which uses them to drive ATP production, and NAD+ is regenerated to go round again.
If you picture the mitochondrion as a power station, NAD+ is the fleet of lorries carrying fuel to the turbines. The lorries are not burnt up in the process, but there need to be enough of them, and they also get borrowed for other jobs. Sirtuins, which help regulate mitochondrial function, and PARP enzymes, which repair DNA, both consume NAD+ as they work. Our explainer What is NAD+ covers those roles in more detail.
Why NAD+ falls, and why that matters for energy
Human tissue studies show NAD+ declining through adult life. A 2012 study in PLoS ONE found levels in the skin of older adults at roughly half those measured in younger adults. The main drivers are rising consumption by the enzyme CD38, which increases with low-grade inflammation, constant demand from DNA repair, and a recycling pathway that becomes less efficient.
Less NAD+ does not switch energy production off. It narrows the margin. A cell with a smaller pool has less to spare when demand spikes after a hard training session, a run of short nights or a long-haul flight, and that is the situation in which people tend to notice slower recovery and an afternoon slump. In animal models, restoring NAD+ improves mitochondrial function and exercise capacity. Whether the same holds for how tired a person feels is the question the human trials try to answer.
What the human trials show
Most human research has used oral precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), rather than NAD+ itself. They consistently raise NAD+ in blood. Their effect on energy and physical performance is less consistent.
| Study | Who and what | Energy or performance finding |
|---|---|---|
| Martens et al., 2018 | 30 healthy adults aged 55 to 79; NR 1000mg a day for 6 weeks | Blood NAD+ rose by about 60%. No significant change in measures of physical function. |
| Dollerup et al., 2018 | 40 men with obesity; NR 2000mg a day for 12 weeks | Well tolerated. No improvement in muscle mitochondrial respiration or insulin sensitivity. |
| Elhassan et al., 2019 | 12 older men; NR 1000mg a day for 21 days | Raised NAD+ metabolites in muscle and reduced inflammatory markers. No change in mitochondrial bioenergetics. |
| Liao et al., 2021 | 48 amateur runners; NMN 300 to 1200mg a day for 6 weeks, with training | Improved aerobic capacity at the ventilatory threshold in the higher-dose groups compared with placebo. |
| Yi et al., 2023 | 80 healthy adults aged 40 to 65; NMN 300 to 900mg a day for 60 days | Blood NAD+ rose and six-minute walking distance increased compared with placebo. |
| Castro-Marrero et al., 2015 | 73 adults with ME/CFS; NADH 20mg plus CoQ10 200mg a day for 8 weeks | Lower perceived fatigue than placebo. Combined product, so the effect cannot be attributed to NADH alone. |
Read together, the pattern is fairly clear. Raising NAD+ is safe at the doses tested and reliably moves blood levels. The trials that measured endurance in active or middle-aged people found modest gains. The trials in sedentary or metabolically unhealthy groups mostly found that NAD+ went up and performance did not. None was large, and most lasted weeks rather than months.
What the research does not show
- No large trial of injected NAD+ for fatigue. Subcutaneous NAD+ has a good safety record and a 2019 infusion study in Frontiers in Aging Neuroscience confirmed that delivered NAD+ is taken up by tissue. But there is no published placebo-controlled trial of injections for tiredness. What people report is real to them, and it is still anecdote.
- No evidence of a stimulant effect. NAD+ does not act on the nervous system the way caffeine does. Anyone expecting a buzz within the hour will be disappointed.
- No evidence it treats a fatigue condition. The ME/CFS study above is interesting, but small, short and based on a combined oral product. It does not show that NAD+ treats chronic fatigue syndrome or any other illness.
The comprehensive 2021 review in Nature Reviews Molecular Cell Biology reaches the same conclusion: the biology is solid, and the human outcome data are still catching up.
Injections vs oral precursors for energy
An injection delivers NAD+ itself rather than a building block, which removes the conversion step through the gut and liver. Subcutaneous bioavailability is above 90%, and small, regular doses keep levels steadier through the week than an occasional large IV drip. That is the practical argument for injections. It is not proof that they produce more energy than capsules, because nobody has run that head-to-head trial. We compare the formats in NAD+ injections vs NMN and NR supplements.
What people tend to notice, and when
Because NAD+ supports a process rather than triggering one, changes tend to be gradual. Based on what customers tell us, and consistent with the mechanism, a realistic picture is:
- First week. Some people notice easier mornings or better sleep. Many notice nothing yet, which is normal.
- Weeks two to four. Steadier energy through the afternoon and quicker recovery after training or a late night are the most common reports.
- Beyond a month. Benefits, if any, depend on consistency. Missing doses for weeks and then taking several at once does not help.
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. Think of it as restoring a resource your cells draw on, not as adding a new one.
Tiredness that needs a doctor, not NAD+
Fatigue is one of the most common reasons people see a GP, and it often has a specific, treatable cause. Before trying NAD+ for tiredness, it is worth ruling these out:
- Iron deficiency or anaemia, vitamin B12 or folate deficiency, and low vitamin D.
- An underactive thyroid, diabetes, or coeliac disease.
- Sleep apnoea, especially if you snore or wake unrefreshed despite long nights.
- Depression, anxiety or prolonged stress.
- Side effects of regular medication, or recovery from a recent infection.
See a doctor promptly if tiredness comes with unexplained weight loss, breathlessness, night sweats or chest pain, or if it has lasted more than a few weeks without an obvious reason. NAD+ is a reasonable thing to explore when those have been checked and the issue is the general flatness that builds up with age and a busy life. The complete UK guide to NAD+ injections covers safety and who should not use it.
Which kit to try for energy
- 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: the NAD+ Discovery Kit includes the pen and two 500mg cartridges, roughly five weeks at the usual rhythm. A month is the shortest period over which most people can judge a change in energy.
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. The full range is in the NAD+ collection.
Frequently asked questions
Does NAD+ give you energy straight away?
Not usually. NAD+ is not a stimulant. It supports how mitochondria make ATP, so any change in energy tends to build over one to four weeks rather than appearing within the hour.
Is there evidence that NAD+ helps with fatigue?
Some. Small trials of oral precursors found better endurance in runners and middle-aged adults, while others found NAD+ rose without any change in performance. There is no large trial of NAD+ injections for fatigue yet.
Can NAD+ help with chronic fatigue syndrome?
It has not been shown to. One small trial of NADH combined with CoQ10 reported lower perceived fatigue in people with ME/CFS, but that is not evidence that NAD+ treats the condition. Anyone with ME/CFS should involve their specialist.
Is NAD+ better than coffee for energy?
They do different things. Caffeine blocks the signals that make you feel tired for a few hours. NAD+ supports the cell's energy machinery over weeks. They can be taken together, and caffeine does not interfere with NAD+.
What time of day should I inject NAD+ for energy?
Most people inject in the morning after a light breakfast, which fits the body's daily rhythm and reduces the chance of mild nausea. Some find a late-evening dose makes it harder to fall asleep.
Why do I still feel tired after starting NAD+?
It can take a few weeks, and NAD+ cannot offset short sleep, low iron or an underactive thyroid. If tiredness persists after a month, or has lasted a long time already, see your GP to rule out other causes.
Sources
- Massudi H et al. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS ONE, 2012.
- Covarrubias AJ et al. NAD+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 2021.
- Martens CR et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 2018.
- Dollerup OL et al. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. American Journal of Clinical Nutrition, 2018.
- Elhassan YS et al. Nicotinamide riboside augments the aged human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures. Cell Reports, 2019.
- Liao B et al. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. Journal of the International Society of Sports Nutrition, 2021.
- Yi L et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience, 2023.
- Castro-Marrero J et al. Does oral coenzyme Q10 plus NADH supplementation reduce fatigue and biochemical parameters in chronic fatigue syndrome? Antioxidants & Redox Signaling, 2015.
- Grant R et al. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Frontiers in Aging Neuroscience, 2019.
