NAD+ vs SS-31 (Elamipretide)
Your cells' master energy currency and anti-aging powerhouse—NAD+ keeps your mitochondria humming, activates longevity genes called sirtuins, and helps repair DNA damage that accumulates as you get older.
A mitochondria-targeting tetrapeptide that binds cardiolipin in the inner mitochondrial membrane. The FDA approved it in September 2025 as FORZINITY, to improve muscle strength in Barth syndrome [8][9]; phase 3 trials in primary mitochondrial myopathy and in dry age-related macular degeneration missed their primary endpoints [13][14].
Written by Michael Carroll — Owner, Director of Research · Reviewed by the Peptide Initiative Research Team · Editorial standards
Quick comparison
Dose range
NAD+
500–500 mg
SS-31 (Elamipretide)
40–40 mg
Frequency
NAD+
Once daily
SS-31 (Elamipretide)
Once daily
Administration
NAD+
Oral (NR or NMN precursors)
SS-31 (Elamipretide)
Subcutaneous injection
Cycle length
NAD+
Ongoing/indefinite
SS-31 (Elamipretide)
Continuous daily use — not cycled
Onset speed
NAD+
Moderate (1-2 weeks)
SS-31 (Elamipretide)
Not established outside Barth syndrome
Evidence level
NAD+
Moderate human trials (Phase 1-2)
SS-31 (Elamipretide)
Strong human trials (Phase 3 or FDA approved)
Benefit ratings
Cellular Energy
Longevity Support
Brain Function
Mitochondrial Protection
Anti-Oxidant (Targeted)
Compound specifications
NAD+
Molecular formula
C21H27N7O14P2
Molecular weight
663.4 g/mol
Half-life
1-2 hours (plasma); tissue levels persist longer
Bioavailability
Variable by route: ~30% oral (precursors), ~100% IV
CAS number
53-84-9
SS-31 (Elamipretide)
Molecular formula
C32H49N9O5
Molecular weight
639.8 g/mol
Half-life
Not stated on the FDA label; peak plasma concentration 0.5-1 hour after subcutaneous injection, ~100% of dose recovered in urine by 48 hours
Bioavailability
~92% (subcutaneous)
CAS number
736992-21-5
Dosing compared
NAD+
Oral
250 mg NR or NMN
Once daily · 4-8 weeks
Lower end of trial-validated oral precursor dosing; NMN 250-900 mg/day and NR from 250 mg/day raise blood NAD+ [1][6].
500 mg NR or NMN
Once or twice daily · Ongoing
500 mg twice daily NR raised PBMC NAD+ ~60% in a randomized placebo-controlled trial in older adults [1][4].
Intravenous
500 mg NAD+ in 500 mL saline
Per infusion — run time is the critical setting, not the milligrams · Studied as 4 consecutive days; no established schedule
Source class: clinical practice. The milligrams alone do not describe this dose; the published studies also state how fast it went in. In the tolerability study, all 6 people (6 of 6, 100%) receiving 500 mg reported moderate to severe abdominal cramping, diarrhoea, nausea, vomiting, increased heart rate, throat pain, congestion and chest pressure during infusion, against 5 of 8 reporting minor tingling and mild cramping on nicotinamide riboside. Participants set their own rate by tolerance; average total infusion time was 97 minutes for NAD+ and 37 minutes for NR [6]. A separate study infused NAD+ at 3 micromoles per minute over 6 hours [7]. Three hours after infusion, blood NAD+ was significantly higher in the NR group than the NAD+ group [6].
SS-31 (Elamipretide)
Subcutaneous
40 mg
Once daily · Continuous — 24 weeks in the phase 3 myopathy trial, up to 168 weeks in the Barth syndrome extension
40 mg once daily is both the starting dose and the maximum. No human trial escalated past it, and it is the approved FORZINITY dose for anyone weighing at least 30 kg [8]. The same flat 40 mg subcutaneous daily dose was used in the 12-patient Barth syndrome trial [6], in MMPOWER-2 (30 patients) [11], in the phase 3 MMPOWER-3 (109 on drug, 109 on placebo) [13] and in ReCLAIM-2 (117 on drug, 59 on placebo) [14]. There is no weight-based subcutaneous dose: the mg/kg figures in circulation are intravenous infusion RATES from MMPOWER-1 [12] and the heart-failure study [7], given in hospital over 2 to 4 hours, and the label states the product is not approved for intravenous use [8]. Halve the dose to 20 mg once daily in adults with an eGFR below 30 mL/min who are not on dialysis; it has not been studied in people on dialysis [8].
Best suited for
NAD+
Healthy Aging Enthusiasts
NAD+ levels naturally decline 50% or more by middle age, and this drop is linked to many signs of aging. Boosting NAD+ helps maintain the cellular repair and energy production that keeps you feeling vital. It's like refilling your cells' gas tanks.
Brain Health Seekers
Your brain is an energy hog—it uses about 20% of your body's energy despite being only 2% of your weight. NAD+ supports the mitochondria that power your neurons, and research shows promising effects on cognitive function and neuroprotection.
Athletes and Active People
Every time you exercise, your muscles burn through NAD+ to produce energy. Boosting your NAD+ levels may help with recovery, endurance, and maintaining muscle function as you age. Many athletes notice improved workout recovery.
Metabolic Support Seekers
NAD+ plays a central role in how your body processes fats and sugars. Research shows it may help support healthy blood sugar levels, improve insulin sensitivity, and support weight management efforts when combined with a healthy lifestyle.
SS-31 (Elamipretide)
Mitochondrial Health Enthusiasts
If you're focused on optimizing cellular energy at the most fundamental level, SS-31 targets the actual machinery inside your mitochondria. It binds to cardiolipin—the special fat molecule that holds your electron transport chain together—keeping your cellular powerhouses running smoothly [1][2].
Aging Adults Concerned About Cellular Decline
Mitochondrial dysfunction is now recognized as a hallmark of aging [18]. Your cells' energy factories get less efficient over time, producing more harmful byproducts. SS-31 helps protect and restore mitochondrial function, addressing one of the root causes of age-related decline [1].
Heart Health Supporters
Your heart is one of the most energy-demanding organs, packed with mitochondria. Clinical trials have studied SS-31 in heart failure patients because cardiac cells are especially vulnerable to mitochondrial dysfunction [1]. Supporting heart mitochondria supports overall cardiovascular function.
Those Recovering from Oxidative Stress
Whether from intense exercise, illness, or environmental factors, oxidative stress damages your mitochondria from the inside out. SS-31 works as an antioxidant exactly where reactive oxygen species are produced—right at the inner mitochondrial membrane—neutralizing them before they cause harm [1].
Side effects
NAD+
Common
- Flushing and warmth
- Digestive upset
- Mild headache
Uncommon
- Increased energy or restlessness
- Vivid dreams
Serious
- Chest tightness during IV infusion
SS-31 (Elamipretide)
Common
- Injection site reactions
Uncommon
- Raised blood eosinophil count
Serious
- Hypersensitivity reaction
- Benzyl alcohol toxicity in neonates
Safety & evidence
NAD+
Evidence level
Moderate human trials (Phase 1-2)
FDA status
Not FDA approved
Safety overview
Two different things are sold as "NAD+": the molecule itself, given by IV, and its oral precursors nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). The published evidence for them is separate. Oral NR has been through randomised trials. A double-blind safety trial in Parkinson's disease tested high-dose NR [3]. Trials have also been run in heart failure with reduced ejection fraction [4] and in older adults with peripheral artery disease [5]. For NAD+ given by IV, one published study compared it directly against NR. Six people received 500 mg of NAD+ by IV and eight received 500 mg of NR, on four consecutive days. All 6 in the NAD+ group (6 of 6) reported moderate to severe abdominal cramping, diarrhoea, nausea, vomiting, increased heart rate, throat pain, congestion and chest pressure during infusion. Five of the 8 in the NR group reported minor tongue, jaw and arm tingling and mild cramping. All symptoms resolved when the infusion finished. Over 30 days, ALT, AST, hsCRP, BUN/creatinine and TSH did not change significantly; alkaline phosphatase fell significantly in the NAD+ group only, remaining within the normal reference range [6]. Participants set their own infusion rate by tolerance. Average total infusion time was 97 minutes for NAD+ against 37 minutes for NR, for the same 500 mg [6]. A separate study infused NAD+ at 3 micromoles per minute over 6 hours, and found plasma NAD+ and its metabolites unchanged until after 2 hours [7]. Three hours after infusion, blood NAD+ was significantly higher in the NR group than in the NAD+ group [6].
Contraindications
- Active cancer (theoretical concern about fueling cancer cell metabolism)
- Pregnancy or breastfeeding
- Known allergy to niacin or B vitamins
- Severe liver disease
SS-31 (Elamipretide)
Evidence level
Strong human trials (Phase 3 or FDA approved)
FDA status
FDA approved as FORZINITY for Barth syndrome (accelerated approval, 19 September 2025); every other use is investigational
Safety overview
In the 24-week phase 3 trial in primary mitochondrial myopathy, adverse events were reported by 98.2% (107 of 109) of participants on elamipretide against 76.1% (83 of 109) on placebo, and injection-site reactions were the only adverse event above 10% in the treated group. Serious adverse events were 4.6% (5 of 109) against 2.8% (3 of 109) and none were judged treatment-related; discontinuation for an adverse event was 7.3% (8 of 109) against 1.8% (2 of 109). There were no deaths and no hospitalisations [13]. In the 12-patient Barth syndrome crossover trial behind the approval, every patient had an injection-site reaction on elamipretide — 12 of 12 (100%) against 8 of 12 (67%) on placebo — with erythema 100% against 25% and induration 67% against 17% [8]. The label carries two warnings: serious hypersensitivity reactions, and benzyl alcohol toxicity, for which the product is not approved in neonates. It also reports blood eosinophil counts rising during treatment, peaking around day 90 and returning to normal over 6 to 12 months [8].
Contraindications
- Serious hypersensitivity to elamipretide or any excipient — the only contraindication on the FDA label
- Neonates — the formulation contains benzyl alcohol
- Pregnancy and breastfeeding — no human data
- Body weight under 30 kg — outside the approved indication and untested
Which is right for you?
Choose NAD+ if...
- Cellular energy and vitality
- Healthy aging and longevity
- Brain health and cognitive support
- Metabolic optimization
Choose SS-31 (Elamipretide) if...
- Mitochondrial health optimization
- Cellular energy enhancement
- Healthy aging support
- Heart health maintenance