NAD+ (nasal spray)

NAD+ (nicotinamide adenine dinucleotide) is the central redox coenzyme of intermediary metabolism and the obligate co-substrate of the sirtuins and PARPs, giving it a dual role in energy transduction and DNA repair. It is a critical cofactor in the electron transport chain, where roughly 90% of ATP is generated. The body holds only about 100 grams of ATP at any time and a moderately active adult turns over approximately body weight in ATP daily, so NAD+ availability sets the ceiling on that turnover.

Endogenous levels decline progressively from roughly the third decade; by the 40s they may be 50% or more below youthful values. The decline is associated with reduced energy output, impaired cellular repair, metabolic dysfunction, and several hallmarks of ageing.

This is the intranasal route, supplied as a refrigerated atomizer. The rationale is bypass of the gastrointestinal tract and first-pass metabolism, which is why no fasted state is required. Onset is reported as anywhere from a few minutes to several hours, a wide window reflecting variable mucosal absorption.

Cycle structure on this route is unusual and deliberate: 12 weeks on with only a 2-week washout — not a typo. That sits against the broader guidance of 8 to 12 weeks on and 4 to 8 weeks off for NAD+ supplementation generally, discussed under dosing.

Alternative routes are subcutaneous or intramuscular injection, oral precursors (niacin, NMN, NR), and lifestyle interventions such as exercise, each with distinct absorption characteristics.

NAD+ cycles between its oxidised form (NAD+) and reduced form (NADH). In glycolysis, the Krebs cycle, and the electron transport chain, NAD+ accepts electrons to become NADH, which donates them at the inner mitochondrial membrane to drive proton pumping and ATP synthesis, regenerating NAD+. Around 90% of ATP arises at this final step. Healthy cells maintain a ratio of roughly 700:1 NAD+ to NADH; when NAD+ is scarce, energy production is rate-limited and cellular stress rises.

Age-related decline has three drivers. NAD+-consuming enzymes, notably CD38 and the PARPs, increase demand as DNA repair and immune processes become less efficient, and CD38 expression rises with age and chronic inflammation. NAMPT, the rate-limiting enzyme of the salvage pathway responsible for about 80% of NAD+ synthesis, loses efficiency. Damaged mitochondria recycle NAD+ less effectively, creating a feed-forward loop of falling NAD+ and rising mitochondrial stress.

NAD+ is also the co-substrate for SIRT1 through SIRT7, which govern DNA repair and genomic stability, inflammation control, mitochondrial biogenesis, fat metabolism and insulin sensitivity, and circadian regulation. PARP-mediated DNA repair consumes NAD+ directly, so accumulating damage plus declining NAD+ is a second vicious cycle.

Intranasal delivery provides NAD+ itself rather than a precursor, so it does not depend on the Preiss-Handler or salvage pathways and avoids gut deamidation of NMN and NR to nicotinic acid. Bilateral administration increases mucosal surface area, reduces pharyngeal runoff, and buffers against the nasal cycle, the physiological alternation in congestion between nostrils that makes single-nostril dosing inconsistent.

NAD+ supplementation supports mitochondrial ATP output, with improved energy and reduced fatigue the most commonly reported effect. Preclinical and early human work suggests improved insulin sensitivity and lipid metabolism. It supplies substrate for PARP-mediated DNA repair and sirtuin signalling in neurons and elsewhere, and preclinical research shows NAD+ replenishment protecting against cardiovascular disease and supporting healthy blood pressure. In clinical settings it has been used to support detoxification from substance dependence under medical supervision.

From the injectable NAD+ entry: healthy-ageing and lifespan effects, increased cellular energy output, increased metabolic rate, neuroprotection against oxidative and ischaemic stress, restoration of mitochondrial function, reduced atherosclerotic plaque, restored arterial elasticity, cognitive maintenance, improved muscle function and skeletal-muscle mitochondrial health, immune support, and sirtuin substrate provision.

A limitation applies: utilising NAD+ and its precursors requires ATP, so with structurally damaged mitochondria the response can be blunted or absent. SS-31 is positioned first in that scenario, with NAD+ layered on once the machinery can use the substrate.

Route-specific content is administration technique. Bilateral splitting maximises mucosal surface area, reduces pharyngeal runoff and swallowing loss, and buffers against the nasal cycle. Head tipped forward, never back; atomizer angled laterally toward the outer canthus; gentle sniff. Head-back administration drives solution into the nasopharynx where it is swallowed rather than absorbed.

Onset per dose is reported as a few minutes to several hours.

First week. Increased energy is commonly reported, with some noting improved sleep quality and mental sharpness. Magnitude tracks baseline NAD+ status; significantly depleted individuals tend to report more pronounced change.

Weeks 2 to 4. Sustained energy improvement, improved exercise recovery, and more perceptible cognitive benefit as repair processes ramp up.

Long term. Cellular effects (DNA repair, mitochondrial support, sirtuin activation) accumulate but are not directly perceptible. Continued use maintains elevated NAD+ and its associated effects.

After stopping. Levels return gradually to baseline with no withdrawal or rebound; benefits diminish over weeks to months.

Non-response. Conversion and utilisation require ATP. With structurally compromised mitochondria the substrate cannot be used efficiently, which accounts for a subset of users reporting no effect. SS-31 is positioned first for the repair phase in that case.

NAMPT suppression. Chronic supplementation can suppress NAMPT, the salvage-pathway enzyme responsible for about 80% of endogenous synthesis; one human study found NR decreased NAMPT despite raising NAD+ metabolites. Stopping after prolonged unbroken use may leave endogenous production below the starting point, which is the rationale for cycling. Exercise increases NAMPT expression and muscle NAD+ by over 100% and supports recovery during the off-cycle.

Morning to early afternoon dosing is preferred; later administration is associated with sleep disturbance in some users.

The nasal figures follow the site's established nasal protocol. Injectable figures for context: loading 100 to 200 mg daily for 7 to 10 consecutive days, maintenance 50 to 100 mg 1 to 3 times per week, morning preferred. Reconstitution guidance is irrelevant to a pre-filled atomizer.

Nasal range 4–20 sprays (20–100 mg) daily on 2–6 days per week, 5 mg per spray, always split bilaterally. Titration is by frequency before amplitude: typical start 4 sprays (20 mg) on 2–3 days per week, then a gradual increase in the number of dosing days at that dose before escalating spray count.

Morning to early afternoon; later dosing may interfere with sleep. No fasted state required. Refrigerate the atomizer.

Cycle: the existing nasal protocol is 12 weeks on, 2 weeks off, explicitly confirmed as not a typo. General NAD+ guidance is 8 to 12 weeks on and 4 to 8 weeks off to prevent NAMPT suppression and allow salvage-pathway recovery, with exercise during the off-cycle. The two have not been reconciled; the longer washout is the conservative reading.

Cumulative exposure: 100 mg on 6 days per week is roughly 2,600 mg per month, under the 3,000 mg monthly ceiling the injectable entry cites for hepatic, renal, and vascular risk, but with a thin margin. Apply the ceiling to the combined total if NAD+ is taken by more than one route.

Administration: bilateral splitting for mucosal surface area, reduced pharyngeal runoff, and buffering against the nasal cycle. Head forward, atomizer angled toward the outer canthus, gentle sniff. Never head-back.

There are no intranasal NAD+ data, and rigorous controlled trials of direct subcutaneous NAD+ are also limited. The evidence base is therefore built on oral precursors.

Precursors raise circulating NAD+. Multiple human trials show oral NMN and NR increase blood NAD+ by 40 to 90%; tissue-level increases are less well characterised. Martens et al., 2018 (Nature Communications) and Elhassan et al., 2019 (Cell Reports) document tolerability and augmentation of the skeletal-muscle NAD+ metabolome in middle-aged and older adults.

Clinical endpoint. Yoshino and colleagues (2021), Science: 10 weeks of NMN at 250 mg daily improved skeletal-muscle insulin sensitivity in overweight or obese women with prediabetes — the strongest single human endpoint available.

Meta-analysis (2024). Li et al., Critical Reviews in Food Science and Nutrition: NMN significantly elevated blood NAD, but body composition, physical performance and most metabolic markers did not differ from control. Biomarker elevation has not translated into consistent clinical benefit.

Enterohepatic conversion. Liu et al., 2024 (Science Advances): NR and NMN are deamidated by gut bacteria to nicotinic acid during absorption, feeding NAD+ synthesis via enterohepatic circulation. A 2025 study in healthy men over 40 found liposomal NMN raised NAD+ significantly more than non-liposomal NMN or placebo.

NAMPT suppression. A human NR study found decreased NAMPT despite elevated NAD+ metabolites. Since the salvage pathway supplies roughly 80% of endogenous NAD+, chronic uninterrupted supplementation may impair endogenous synthesis — the mechanistic basis for cycling. Exercise raises NAMPT expression by over 100% and muscle NAD+ by over 100%.

Preclinical. Animal models show extended lifespan and healthspan and reversal of some age-related decline; human translation is unproven. Whether intranasal delivery reproduces the bypass of gut deamidation attributed to injection has not been studied.