NAD Therapy Side Effects: What to Know Before Your IV or Injection

How NAD Therapy Is Administered

NAD therapy is typically delivered in two ways:

• IV infusions (“NAD IV therapy”) – a solution containing NAD⁺ (or related compounds) is slowly administered via intravenous drip by a trained clinician. 
• Injections or “NAD shots” – NAD⁺ is given via direct injection, often subcutaneously or intramuscularly.
  

Both methods bypass the digestive system, delivering NAD⁺ directly into the bloodstream, which proponents argue may offer faster bioavailability and support cellular energy metabolism, mitochondrial function, and recovery.

Because NAD⁺ is not an FDA-approved drug for most of these applications, these treatments remain largely off-label or considered “wellness interventions.” Patients and providers must rely on available evidence and exercise caution.

Evidence-Based Side Effects of NAD Therapy

While early data and user reports suggest many NAD infusions are tolerated reasonably well, the literature also identifies mild, moderate, and rare adverse effects, as well as unknowns around long-term safety.

What Research Says

A 2023 systematic review of NAD (and NADH) supplementation in humans — covering 489 participants — reported generally good tolerability. [1]

Commonly reported side effects included:

• Muscle pain
• Nervous system disturbances
• Fatigue
• Sleep disruption
• Headaches

Importantly, none of the reviewed trials documented serious or life-threatening reactions. 

Other analyses caution that boosting NAD⁺ levels through precursors or direct infusion could theoretically alter methylation, genome repair pathways (e.g., PARPs), or oxidative stress regulation, especially at high doses or with frequent use. [2]

Because of limited long-term human data, experts describe the full safety profile of NAD therapy as unknown at this point. 

Side Effects Categorized by Severity

Here’s a breakdown of what side effects have been reported, organized by frequency and seriousness.

Mild (Common / Temporary)

These are the most frequently reported effects, typically resolving within hours to a day:

• Flushing or warmth/redness — often due to infusion rate triggering a “niacin-like flush.” Slowing the drip usually resolves it.

• Nausea or mild gastrointestinal discomfort — even though the nutrient bypasses digestion, some patients still comment on queasiness or stomach unease during or immediately after infusion.

• Headache, light-headedness, or fatigue — common, especially during initial sessions; sometimes attributed to fluid shifts or metabolic adjustment.

• Vein discomfort / mild injection-site irritation — redness, mild pain, or soreness at the IV site may occur, especially for those with sensitive veins or when infusions are given rapidly.

Moderate (Less Frequent / Dose- or Protocol-Dependent)

These are less common and often related to infusion speed, dosage, or individual sensitivity:

• Dizziness, low blood pressure, or lightheadedness — due to fluid volume shifts or changes in vascular tone. Some consent forms warn about possible blood pressure fluctuations.

• Transient metabolic or glucose changes — a small number of reports link NAD therapy to temporary changes in blood sugar or glucose regulation; people with diabetes or insulin-related conditions should be especially cautious.

• Inflammation markers or mild immune activation — a minority of users show temporary rises in inflammatory markers after IV NAD, though clinical significance remains uncertain.

Rare (Uncommon but Potentially Serious)

Although rare, some clinics and case reports include more serious adverse events or risks — especially when therapy is frequent, high-dose, or administered in non-medical settings:

• Vein inflammation (phlebitis), infiltration or extravasation — when IV solution leaks into surrounding tissue instead of vein, leading to irritation, pain, or local tissue damage. 
• Infection at IV site — as with any IV treatment, there is a risk of infection if sterility protocols are not strictly followed. 
• Potential metabolic or cellular stress over time — preclinical warnings suggest repeated NAD elevation may affect DNA repair pathways or methylation balance, possibly carrying theoretical long-term risks. [3] 
• Allergic or hypersensitivity reactions — in rare cases, individuals may react to preservatives or additives in compounded NAD solutions; severe reactions (anaphylaxis) are very uncommon but have been described in informed-consent documentation.

Long-Term Safety & Precautions

Because most human studies assessing NAD or NADH supplementation remain short-term and small in scale, long-term safety remains uncertain. A recent review pointed out that while short-term adverse events are generally mild, the potential for long-term issues — especially with frequent, high-dose infusions — cannot be excluded. [4]

Given that NAD⁺ plays a role in cellular metabolism, DNA repair, and inflammation regulation, some researchers have raised theoretical concerns about overloading the system, possibly leading to imbalanced methylation, oxidative stress, or unintended cellular signaling effects. [5]

Because of these unknowns, many experts recommend:

• Conservative dosing

• Avoiding frequent long-term infusions

• Regular monitoring (blood work, metabolic panels) if undergoing repeated therapy

Who Should Avoid or Use Extra Caution with NAD Therapy?

Before scheduling NAD IV therapy or injections, individuals should discuss their suitability with a licensed clinician. Special caution is advised for:

• Pregnant or breastfeeding individuals — there is limited safety data for NAD supplementation in these populations.

• People with kidney or liver impairment, congestive heart failure, or fluid-balance disorders — risk of fluid overload or impaired clearance.

• Individuals with uncontrolled blood pressure or cardiovascular disease — infusion-related vascular changes may pose risks.

• Anyone with a history of severe allergies or sensitivity to IV medications/compounds — higher risk of infusion reactions.

• People on medications that affect metabolism or mitochondria, including some antidiabetic drugs, liver-metabolized medications, or chemotherapy — because interactions are not well studied.

Safety & Professional Guidance

Properly administered NAD therapy should always follow medical protocols:

• Delivered by licensed medical professionals (RN, NP, MD) in a controlled, sterile setting.

• Comprehensive pre-screening: medical history, medications, allergies, and baseline labs.

• Informed consent, including disclosure that NAD therapy is not FDA-approved for anti-aging, detox, or disease treatment.

• Continuous monitoring during infusion, with the ability to stop or adjust the drip rate if side effects arise.

• Follow-up care and lab monitoring if undergoing repeated sessions.
  

NAD therapy can be considered a supplemental wellness practice, not a substitute for a balanced lifestyle, proper nutrition, physical activity, or medically indicated treatments.

Summary

NAD therapy — whether via IV drip or injection — offers potential benefits for energy, recovery, and wellness. But like any medical intervention, it carries risks and uncertainties, particularly because long-term safety data remain limited.

Evidence suggests that when administered properly by licensed professionals, NAD⁺ infusions are generally well tolerated, with mainly mild and temporary side effects such as flushing, nausea, or headache. However, moderate or rare risks including vein irritation, metabolic changes, or allergic reactions exist — especially in high-risk individuals or with repeated use.

Before proceeding, individuals should undergo medical screening, informed consent, and professional monitoring. NAD therapy should complement — not replace — a healthy lifestyle, proper nutrition, regular medical care, and evidence-based treatments.

If you’d like to explore NAD therapy under a careful, medically supervised program, including monitoring and safety protocols, learn more about Drip Hydration’s NAD+ IV therapy and treatment options. 

Live well, stay informed, and always prioritize safety.

References:

[1] National Library of Medicine, Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review, Gindri, I.D., Ferrari, G., Pinto, L.P.S., Bicca., J., Dos Santos, I.K., Dallacosta, D., de Mello Roesler, C.R., April 2024

[2] PubMed, Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment, Hwang, E.S., Song, S.B., April 2020

[3] [4] [5] National Library of Medicine, NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis, Braidy, N., Liu, Y., April 2020