💡 What You Need to Know Right Away
- A systematic review of 10 RCTs with 489 participants found NAD supplementation safe with low incidence of serious side effects[Evidence: A][1]
- Analysis of 147 studies (113 preclinical, 34 clinical) shows NAD+ precursors favorable for age-related disorders involving oxidative stress and mitochondrial dysfunction[Evidence: A][2]
- IV NAD+ infusions showed significant relationships with decreasing craving scores, anxiety, and depression in substance use disorder patients[Evidence: C][3]
- Clinical trials demonstrate NAD+ precursor supplementation results in 2.6-fold increase in blood NAD+ levels (p<0.001)[Evidence: B][7]
You've likely heard about NAD+ IV therapy from wellness clinics, celebrity endorsements, or longevity podcasts. The promise sounds compelling: boost your cellular energy, sharpen your mind, and potentially slow aging—all through an intravenous infusion. But what does the science actually say?
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every cell of your body, essential for energy production and cellular repair. As you age, NAD+ levels naturally decline, which has sparked intense interest in supplementation strategies. This guide examines 17 peer-reviewed studies to help you understand what NAD+ IV therapy can realistically offer—and where the evidence falls short.
Whether you're exploring NAD+ therapy for chronic fatigue, cognitive support, or anti-aging benefits, you deserve honest, evidence-based information. Let's separate the science from the marketing claims.
❓ Quick Answers
What is NAD+ IV therapy?
NAD+ IV therapy is a treatment that delivers nicotinamide adenine dinucleotide directly into the bloodstream through intravenous infusion. This coenzyme plays essential roles in cellular energy production, DNA repair, and metabolism. The IV delivery method bypasses the digestive system, allowing for direct blood absorption.[Evidence: A][2]
What are the benefits of NAD+ IV therapy?
Research suggests NAD+ supplementation may support cellular energy production, cognitive function, and age-related health concerns. A systematic review found benefits for conditions involving chronic oxidative stress, inflammation, and impaired mitochondrial function, including potential applications for Parkinson's, prediabetes, and Alzheimer's disease.[Evidence: A][2]
How long does NAD+ IV therapy last?
Clinical protocols typically involve IV NAD+ 500-1000 mg daily for 4 days initially, followed by twice weekly sessions for one month, then transitioning to twice monthly maintenance sessions. The duration of effects varies by individual and treatment goal.[Evidence: C][3]
Is NAD+ IV therapy safe?
A systematic review analyzing 10 randomized controlled trials with 489 participants found NAD/NADH supplementation safe with low incidence of side effects. Most reported effects were not serious and included muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches.[Evidence: A][1]
How much does NAD+ IV therapy cost?
NAD+ IV therapy typically costs $250-$400 for 250mg sessions, $400-$700 for 500mg sessions, and $600-$1,500 for 1000mg sessions. Costs vary by geographic location and provider. Most insurance plans do not cover NAD+ IV therapy as it is considered an off-label treatment.
What are the side effects of NAD+ IV therapy?
Common side effects from NAD supplementation studies include muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches—none classified as serious adverse events. Side effects typically resolve by slowing the infusion rate.[Evidence: A][1]
How often should you get NAD+ IV therapy?
Clinical protocols for substance use disorder used IV NAD+ daily for 4 days initially, then twice weekly for one month, transitioning to twice monthly maintenance. Optimal frequency for other applications has not been established in controlled trials.[Evidence: C][3]
Does NAD+ IV therapy really work?
NAD supplementation shows promise in limited studies. A systematic review found promising yet speculative results for age-related conditions, but noted the need for longer-term human trials. Most clinical evidence exists for oral precursors rather than IV delivery specifically.[Evidence: A][5]
🔬 How Does NAD+ IV Therapy Work?
Think of NAD+ as your cells' universal battery charger. Just as your phone needs electricity to function, your cells need NAD+ to convert food into usable energy. Without adequate NAD+, your cellular "devices" start running on low power—affecting everything from brain function to muscle recovery.
At the molecular level, NAD+ serves as a critical coenzyme in cellular metabolism. Research has identified NAD+ metabolism modulation as a therapeutic approach using vitamin B3 precursors for age-related conditions.[Evidence: D][12] The compound participates in over 500 enzymatic reactions in your body.
The Sirtuin Connection
NAD+ activates a family of proteins called sirtuins, which act like cellular repair crews. Animal studies demonstrate that NAD+ rescued cognitive deficits through the Sirt1/PGC-1α pathway, reduced reactive oxygen species (ROS) production, and inhibited pro-inflammatory markers IL-1β and TNF-α.[Evidence: C][4]
Imagine sirtuins as quality control inspectors in a factory. When NAD+ levels are sufficient, these inspectors can identify damaged DNA and cellular components, flagging them for repair or removal. When NAD+ declines with age, fewer inspectors are "on duty," allowing cellular damage to accumulate.
Mitochondrial Function
NAD+ precursors appear favorable for age-related disorders characterized by chronic oxidative stress, inflammation, and impaired mitochondrial function. A comprehensive analysis of 147 articles (113 preclinical, 34 clinical studies) identified potential benefits for Parkinson's disease, metabolic conditions including overweight and prediabetes, and Alzheimer's disease.[Evidence: A][2]
Cognitive and Neurological Pathways
NAD+ precursor supplementation has been identified as a promising strategy for cognitive impairment across multiple disease contexts, including Alzheimer's disease, vascular dementia, diabetes-related cognitive decline, stroke, and traumatic brain injury. However, researchers note a significant gap between preclinical promise and human clinical evidence.[Evidence: D][6]
Research examining NAD+ precursors for Alzheimer's disease included analysis of NMN (3 preclinical studies) and NR (4 preclinical studies), with 2 human clinical trials showing improvements.[Evidence: A][13]
Addiction and Reward Pathways
Raising intracellular NAD+ levels has been identified as a potential target for managing addictive behavior, with research suggesting it may reduce cravings and withdrawal symptoms.[Evidence: D][9]
Reproductive Health
Research indicates NAD+ precursor treatment restores female reproductive capacity in aging animal models, suggesting potential applications for fertility support.[Evidence: B][15]
IV Delivery Mechanism
Animal studies confirm that intravenous administration of NAD+ precursors (specifically nicotinamide riboside) successfully raised skeletal muscle NAD+ levels, though notably did not affect respiratory capacity or insulin sensitivity in these models.[Evidence: C][11]
📊 Dosage and Treatment Protocols
Dosage protocols vary significantly based on treatment goals and delivery method. The only IV-specific dosing data comes from substance use disorder research, while most clinical trials have studied oral NAD+ precursors.
| Purpose/Condition | Dosage | Frequency/Duration | Delivery | Evidence |
|---|---|---|---|---|
| Substance use disorder (initial phase) | 500-1000 mg | Daily for 4 days | IV | [C][3] |
| Substance use disorder (active treatment) | 500-1000 mg | Twice weekly for 1 month | IV | [C][3] |
| Substance use disorder (maintenance) | 500-1000 mg | Twice monthly | IV | [C][3] |
| Mild cognitive impairment (NR) | 1000 mg | Daily for 10 weeks | Oral | [B][7] |
| Healthy aging (NMN - low dose) | 300 mg | Daily for 60 days | Oral | [B][16] |
| Healthy aging (NMN - medium dose) | 600 mg | Daily for 60 days | Oral | [B][16] |
| Healthy aging (NMN - high dose) | 900 mg | Daily for 60 days | Oral | [B][16] |
What the Data Shows
In the NR trial with 20 participants over 10 weeks at 1 g/day, researchers observed a 2.6-fold increase in blood NAD+ (p<0.001), while neurocognitive metrics remained stable. The treatment was well tolerated with no adverse events.[Evidence: B][7]
The NMN trial with 80 participants over 60 days found blood NAD+ statistically significantly increased in all NMN-treated groups, with improved physical performance. The supplement was safe and well-tolerated across all dose levels tested.[Evidence: B][16]
Important Dosage Limitations
Optimal IV NAD+ dosing for general wellness, anti-aging, or cognitive enhancement has not been established through controlled trials. The only IV-specific dosing data comes from substance use disorder research (500-1000 mg). Most RCT data is for oral precursors (NR, NMN), not IV NAD+ directly.
⚠️ Risks, Side Effects, and Warnings
Side Effects by Frequency
A systematic review analyzing 10 RCTs with 489 participants found NADH supplementation safe with low incidence of side effects. Reported side effects included muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches—none classified as serious adverse events.[Evidence: A][1]
The IV NAD+ case series in substance use disorder patients reported limited toxic effects at doses of 500-1000 mg.[Evidence: C][3]
Drug Interactions
No significant drug interactions were documented in the clinical trials reviewed. However, specific interaction studies have not been conducted. Inform your healthcare provider of all medications before starting NAD+ therapy.
Contraindications
Research on NAD deficiency indicates that NAD deficiency during pregnancy causes congenital NAD deficiency disorder (CNDD) with multiple congenital malformations, though dietary supplements can prevent CNDD.[Evidence: D][10] This suggests NAD+ itself is important during pregnancy, but IV NAD+ therapy safety during pregnancy has not been studied.
Monitoring Recommendations
Specific monitoring protocols have not been established in clinical trials. General recommendations include monitoring for adverse reactions during and after infusion. Consult your healthcare provider for individualized monitoring guidance.
🥗 Practical Ways to Use NAD+ IV Therapy
How to Use This in Your Daily Life
Scenario 1: Substance Use Disorder Support
- Dose: 500-1000 mg IV NAD+[3]
- Duration: 4 days initial, then twice weekly for 1 month, then twice monthly maintenance[3]
- Population: Adults with substance use disorder
- What to track: Craving scores, anxiety levels, depression symptoms
- Expected results: Significant relationships observed between IV NAD+ infusions and decreasing craving scores, anxiety, and depression[3]
General Wellness (Limited Data)
Why dosage is unclear: No RCTs have established optimal IV NAD+ dosing for general wellness, anti-aging, or cognitive enhancement. Most clinical evidence comes from oral precursor studies (NR, NMN) rather than IV NAD+.
What we know: Oral NAD+ precursors at 300-1000 mg daily have been studied for 8-10 weeks with good safety profiles and measurable increases in blood NAD+ levels.[7][16]
Practical Integration
IV NAD+ therapy requires administration at a medical facility with qualified personnel. Sessions typically last 1.5-5 hours depending on dose. Store any oral NAD+ precursor supplements in a cool, dry place away from direct sunlight.
Common Mistakes to Avoid
- Expecting immediate dramatic results: Clinical studies measured outcomes over weeks to months—not hours or days.
- Skipping medical consultation: IV therapy should be administered under medical supervision with proper screening.
- Inconsistent treatment: The substance use disorder protocol required consistent sessions over time[3]—sporadic use may not achieve benefits.
- Ignoring oral alternatives: Oral precursors (NR, NMN) have more RCT data than IV NAD+ and may be appropriate for many goals.
⚖️ NAD+ IV Therapy vs. Oral NAD+ Supplements
One of the most important decisions in NAD+ supplementation is choosing between IV delivery and oral precursors (NR or NMN). Here's how they compare based on available evidence:
| Feature | NAD+ IV Therapy | Oral NR/NMN |
|---|---|---|
| RCT Evidence | Limited (1 case series for SUD)[3] | Multiple RCTs (20-80 participants)[7][16] |
| Blood NAD+ Increase | Not measured in available studies | 2.6-fold increase documented (p<0.001)[7] |
| Convenience | Clinic visit required, 1.5-5 hours | At-home, daily capsule |
| Typical Cost | $500-1,500 per session | $40-100 per month |
| Safety Data | Limited toxic effects at 500-1000 mg[3] | Safe and well-tolerated in multiple RCTs[1][16] |
| Study Duration | Up to 1 month (SUD protocol) | Up to 10 weeks[7] |
| Studied Applications | Substance use disorder[3] | Cognitive function, healthy aging, long-COVID[7][14][16] |
Key Comparison Insights
Oral NAD+ precursors have substantially more RCT data than IV NAD+. The systematic review of NAD supplementation included mostly oral studies and noted the need for longer-term human trials.[Evidence: A][5]
Animal studies confirm IV administration of NAD+ precursors can raise tissue NAD+ levels[11], but human pharmacokinetic comparisons between IV and oral routes remain limited.
What The Evidence Shows (And Doesn't Show)
What Research Suggests
- NAD supplementation is safe with low incidence of side effects based on 10 RCTs with 489 participants[1]
- NAD+ precursors appear favorable for age-related disorders involving oxidative stress and mitochondrial dysfunction based on 147 articles analyzed (113 preclinical, 34 clinical)[2]
- Oral NAD+ precursors produce measurable 2.6-fold increase in blood NAD+ levels (p<0.001) in RCTs[7]
- IV NAD+ infusions showed significant relationships with decreasing craving scores, anxiety, and depression in substance use disorder (case series, n=50)[3]
- 8-week NR supplementation produced 7% reduction in pTau217 Alzheimer's biomarker versus placebo[17]
What's NOT Yet Proven
- IV NAD+ RCT data: No randomized controlled trials exist specifically for IV NAD+ therapy—only one case series (Evidence Level C)
- Optimal IV dosing: Dosing for general wellness, anti-aging, or cognitive enhancement not established—only SUD protocol (500-1000 mg) has been published
- Long-term safety: Maximum study duration was 10 weeks—chronic use safety beyond this timeframe is unknown
- Cognitive enhancement in healthy adults: NR did not significantly improve cognition, fatigue, sleep, or mood versus placebo in long-COVID RCT despite raising NAD+ levels 2.6-3.1-fold[14]
- Gap between preclinical and clinical: Researchers explicitly note a gap between preclinical promise and human clinical evidence[6]
Where Caution Is Needed
- Elevated NAD+ ≠ clinical benefit: One RCT showed NR elevated NAD+ 2.6-3.1-fold but did not significantly improve cognition, fatigue, sleep, or mood versus placebo[14]
- Conflict of interest: The IV NAD+ substance use disorder study (Source 3) disclosed that the investigator holds patents on enkephalinase therapy components
- Results characterized as "speculative": Systematic review authors described findings as "promising yet speculative" and emphasized need for longer-term human trials[5]
- IV-specific data limited: Animal studies confirm IV raises tissue NAD+[11], but most human evidence is for oral precursors
Should YOU Try This?
Best suited for: Individuals with substance use disorder seeking adjunctive support (has clinical evidence[3]); those who have tried oral precursors without satisfactory results; individuals under medical supervision seeking NAD+ elevation
Not recommended for: Pregnant or breastfeeding women (IV safety unstudied); individuals seeking proven anti-aging or cognitive enhancement (evidence speculative); those unable to afford ongoing sessions ($500-1,500 each); anyone expecting dramatic immediate results
Realistic timeline: Substance use disorder protocol required 4 daily sessions initially, then twice weekly for a month[3]; oral precursor studies measured outcomes at 8-10 weeks[7][16]
When to consult a professional: Before starting any NAD+ therapy; if taking medications (interactions unstudied); if you have underlying health conditions; if pregnant, breastfeeding, or planning pregnancy
Frequently Asked Questions
Is NAD+ IV therapy worth it?
The value of NAD+ IV therapy depends on your specific goals and circumstances. For substance use disorder, clinical evidence shows significant relationships between IV NAD+ infusions and decreasing craving scores, anxiety, and depression. For general wellness or anti-aging, the evidence is less clear. Oral NAD+ precursors (NR, NMN) have more RCT data, are considerably less expensive ($40-100/month vs. $500-1,500/session), and can be taken at home. Consider whether the specific benefits you seek have evidence supporting IV delivery versus oral alternatives.
What is the difference between NAD+ IV therapy and oral supplements?
NAD+ IV therapy delivers nicotinamide adenine dinucleotide directly into your bloodstream, while oral supplements provide NAD+ precursors (typically NR or NMN) that your body converts to NAD+. Oral NR supplementation at 1 g/day for 10 weeks produced a 2.6-fold increase in blood NAD+ (p<0.001) in an RCT with 20 participants. IV delivery bypasses digestion, but human studies directly comparing bioavailability between routes are limited. Oral precursors have more RCT data across multiple health applications.
How long does a NAD+ IV session take?
NAD+ IV sessions typically range from 1.5 to 5 hours depending on the dose administered. Lower doses (250mg) generally take 1.5-2 hours, while higher doses (1000mg) may require 3-5 hours. The clinical protocol for substance use disorder used 500-1000 mg daily for 4 days initially. Infusion rate may be slowed if side effects occur, potentially extending session duration. Individual factors affect infusion time—discuss with your provider.
Who should not get NAD+ IV therapy?
Specific contraindications for NAD+ IV therapy have not been established through controlled trials. Research notes that NAD deficiency during pregnancy can cause congenital NAD deficiency disorder (CNDD) with multiple malformations—meaning NAD+ itself is important, but IV therapy safety during pregnancy is unstudied. General caution applies to pregnant or breastfeeding women, individuals on multiple medications, and those with serious underlying health conditions. Always consult a healthcare provider before starting IV therapy.
Can NAD+ IV therapy help with addiction?
Research suggests raising intracellular NAD+ levels may be a potential target for managing addictive behavior, potentially reducing cravings and withdrawal symptoms. A case series of 50 patients with substance use disorder found significant relationships between IV NAD+ infusions (500-1000 mg) and decreasing craving scores, anxiety, and depression. However, this was a case series (Evidence Level C), not a randomized controlled trial. More rigorous research is needed to confirm these findings.
Does NAD+ IV therapy help with anti-aging?
NAD+ precursors show promise for age-related conditions. A systematic review of 147 articles (113 preclinical, 34 clinical) found NAD+ precursors favorable for disorders involving chronic oxidative stress, inflammation, and impaired mitochondrial function—including Parkinson's, metabolic conditions, and Alzheimer's. An 8-week NR supplementation study showed a 7% reduction in pTau217 biomarker (associated with Alzheimer's) versus placebo. However, researchers note the need for longer-term human trials, and results remain 'promising yet speculative.'
What is the best dosage for NAD+ IV therapy?
The only IV NAD+ dosing data from clinical research comes from substance use disorder studies using 500-1000 mg daily for 4 days, then twice weekly for one month, then twice monthly maintenance. Optimal dosing for other applications (anti-aging, cognitive enhancement, general wellness) has not been established through controlled trials. Most RCT data is for oral precursors: NR at 1000 mg/day for 10 weeks and NMN at 300-900 mg/day for 60 days.
Our Accuracy Commitment and Editorial Principles
At Biochron, we take health information seriously. Every claim in this article is supported by peer-reviewed scientific evidence from reputable sources published in 2015 or later. We use a rigorous evidence-grading system to help you understand the strength of research behind each statement:
- [Evidence: A] = Systematic review or meta-analysis (strongest evidence)
- [Evidence: B] = Randomized controlled trial (RCT)
- [Evidence: C] = Cohort or case-control study
- [Evidence: D] = Expert opinion or clinical guideline
Our editorial team follows strict guidelines: we never exaggerate health claims, we clearly distinguish between correlation and causation, we update content regularly as new research emerges, and we transparently note when evidence is limited or conflicting. For our complete editorial standards, visit our Editorial Principles page.
This article is for informational purposes only and does not constitute medical advice. Always consult qualified healthcare professionals before making changes to your health regimen, especially if you have medical conditions or take medications.
References
- 1 . Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review, Gindri IM et al., American Journal of Physiology - Endocrinology and Metabolism, 2024, Vol. 326(4): E417-E427, PubMed, DOI [Evidence: A]
- 2 . NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis, Braidy N, Liu Y, Experimental Gerontology, 2020, Vol. 132: 110831, PubMed, DOI [Evidence: A]
- 3 . Nicotinamide Adenine Dinucleotide (NAD+) and Enkephalinase Inhibition (IV1114589NAD) Infusions Significantly Attenuate Psychiatric Burden Sequalae in Substance Use Disorder (SUD) in Fifty Cases, Blum K et al., Current Psychiatry Research and Reviews, 2022, Vol. 18(2): 125-143, PubMed, DOI [Evidence: C]
- 4 . NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway, Zhao Y et al., Journal of Neuroinflammation, 2021, Vol. 18(1): 207, PubMed, DOI [Evidence: C]
- 5 . Clinical Evidence for Targeting NAD Therapeutically, Radenkovic D, Reason, Verdin E, Pharmaceuticals (Basel), 2020, Vol. 13(9), PubMed, DOI [Evidence: A]
- 6 . Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts, Campbell JM, Nutrients, 2022, Vol. 14(15), PubMed, DOI [Evidence: D]
- 7 . A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment, Orr ME et al., GeroScience, 2024, Vol. 46(1): 665-682, PubMed, DOI [Evidence: B]
- 8 . NR Supplementation During Lactation: Benefiting Mother and Child, Yang D, Wan Y, Trends in Endocrinology and Metabolism, 2019, Vol. 30(4): 225-227, PubMed, DOI [Evidence: D]
- 9 . Sobriety and Satiety: Is NAD+ the Answer?, Braidy N, Villalva MD, van Eeden S, Antioxidants (Basel), 2020, Vol. 9(5), PubMed, DOI [Evidence: D]
- 10 . Nicotinamide Adenine Dinucleotide Deficiency and Its Impact on Mammalian Development, Dunwoodie SL et al., Antioxidants & Redox Signaling, 2023, Vol. 39(16-18): 1108-1132, PubMed, DOI [Evidence: D]
- 11 . Intravenous nicotinamide riboside elevates mouse skeletal muscle NAD+ without impacting respiratory capacity or insulin sensitivity, Damgaard MV et al., iScience, 2022, Vol. 25(2): 103863, PubMed, DOI [Evidence: C]
- 12 . The role of NAD+ metabolism and its modulation of mitochondria in aging and disease, Yusri K et al., npj Metabolic Health and Disease, 2025, Vol. 3(1): 26, PubMed, DOI [Evidence: D]
- 13 . Supplementation with NAD+ Precursors for Treating Alzheimer's Disease: A Metabolic Approach, Alghamdi M, Braidy N, Journal of Alzheimer's Disease, 2024, Vol. 101(s1): S467-S477, PubMed, DOI [Evidence: A]
- 14 . Effects of nicotinamide riboside on NAD+ levels, cognition, and symptom recovery in long-COVID: a randomized controlled trial, Wu CY et al., EClinicalMedicine, 2025, Vol. 89: 103633, PubMed, DOI [Evidence: B]
- 15 . NAD+ Repletion Rescues Female Fertility during Reproductive Aging, Bertoldo MJ et al., Cell Reports, 2020, Vol. 30(6): 1670-1681.e7, PubMed, DOI [Evidence: B]
- 16 . 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, Yi L et al., GeroScience, 2023, Vol. 45(1): 29-43, PubMed, DOI [Evidence: B]
- 17 . Cognitive and Alzheimer's disease biomarker effects of oral nicotinamide riboside (NR) supplementation in older adults with subjective cognitive decline and mild cognitive impairment, Wu CY et al., Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2025, Vol. 11(1): e70023, PubMed, DOI [Evidence: B]
Medical Disclaimer
This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician. All readers are advised to consult their doctors or qualified health professionals regarding specific health questions and before making any changes to their health routine, including starting new supplements.
Neither Biochron nor the author takes responsibility for possible health consequences of any person reading or following the information in this educational content. All readers, especially those taking prescription medications, should consult their physicians before beginning any nutrition, supplement, or lifestyle program.
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