What Are the Negatives of NAD+? Understanding the Risks and Side Effects

November 18, 2025 •

4 min read

Cellular NAD+ levels decline by an estimated 10-80% as we age, fueling a booming market for supplements and therapies promising to restore youthful vitality. However, what are the negatives of NAD+ that these marketing campaigns often overlook? While generally safe in the short term, potential risks and adverse effects warrant a closer look before starting supplementation.

Quick Summary

NAD+ supplementation can cause mild side effects like nausea and headaches, with potential risks such as liver stress and metabolic disruption, especially at high doses. Long-term safety data is limited, and specific groups, including cancer patients and those with pre-existing conditions, should exercise caution.

Key Points

Mild Side Effects are Common: Users often report mild issues like nausea, headaches, fatigue, and flushing, which may vary depending on the delivery method (oral vs. IV).
Cancer Risk is a Major Concern: While not proven to cause cancer, boosting NAD+ levels could potentially fuel the growth of existing cancer cells, making consultation with an oncologist critical for those with a cancer history.
Potential for Metabolic and Liver Strain: High doses, particularly of certain precursors, have been linked to decreased insulin sensitivity and elevated liver enzymes in studies.
Lack of Long-Term Human Safety Data: Most evidence is from small, short-term trials, and the long-term effects and safety of chronic NAD+ supplementation in humans remain largely unknown.
Risk of Harmful Drug Interactions: NAD+ supplements can interact with medications for blood pressure, diabetes, and depression, necessitating medical clearance before use.
Natural Alternatives Offer a Safer Approach: Lifestyle changes like regular exercise and a healthy diet can increase NAD+ levels naturally without the risks associated with excessive supplementation.

Common Side Effects of NAD+ Supplementation

Whether taken orally as a precursor supplement (like Nicotinamide Riboside or Nicotinamide Mononucleotide) or administered via intravenous (IV) therapy, NAD+ can cause a range of side effects. Most are mild and temporary, though they depend on the dosage, delivery method, and individual response.

Oral Supplementation Side Effects

Gastrointestinal Issues: Mild nausea, bloating, abdominal discomfort, and diarrhea are reported by some users.
Headaches and Fatigue: While boosters are meant to increase energy, some individuals experience headaches or unusual fatigue.
Flushing and Rashes: Certain precursors, particularly older forms of niacin, are known to cause skin flushing, a warm, red sensation on the skin, along with itching or rashes.

NAD+ IV Therapy Side Effects

IV administration delivers NAD+ directly into the bloodstream, sometimes leading to more intense, but still temporary, reactions.

Infusion Site Reactions: Common reactions include redness, swelling, bruising, or tenderness at the injection site.
Temporary Discomfort: Rapid infusion rates can cause nausea, abdominal cramping, chest pressure, and dizziness, which usually resolve when the rate is slowed.
Blood Pressure Fluctuations: Some individuals, particularly those sensitive to blood pressure changes, may experience temporary drops.

Significant Risks and Contraindications

While not common, certain individuals face elevated risks when supplementing with NAD+, especially concerning pre-existing health conditions or medication use. Professional medical guidance is essential to mitigate these dangers.

Cancer-Related Concerns

One of the most debated negatives of NAD+ is its potential interaction with cancer. While boosting NAD+ does not cause cancer, the concern is that it could help fuel the growth and proliferation of existing cancer cells, as cancer cells often have high energy demands. This is not a confirmed outcome in humans, but animal studies have raised cautionary flags, and some NAD+ consuming enzymes are overexpressed in various cancers.

Individuals with a personal or strong family history of cancer should consult an oncologist before considering NAD+ supplementation.

Metabolic and Organ Strain

High doses of NAD+ precursors, especially nicotinamide (NAM), have shown concerning metabolic and organ-related effects in studies.

Decreased Insulin Sensitivity: In human studies, high doses of NAM (2g daily) have been linked to decreased insulin sensitivity in just two weeks. This poses a risk for individuals with diabetes or prediabetes, potentially interfering with blood sugar regulation.
Liver Toxicity: The liver is crucial for processing NAD+ precursors, and high levels can cause stress. Elevated liver enzymes have been reported in some cases, and animal studies suggest potential hepatotoxicity at high doses of NAM.
Methylation Disruption: The breakdown of some NAD+ precursors uses up methyl groups, which are vital for many cellular processes, including DNA expression. High doses could theoretically disrupt the body's methylation balance, though short-term human trials have not shown significant impact.

Important Drug Interactions

NAD+ supplements can interact with several medications, potentially altering their effectiveness or causing adverse effects.

Blood Pressure Medications: Since NAD+ can influence blood pressure, combining it with antihypertensive drugs could cause a dangerous drop in blood pressure.
Diabetes Medications: The potential for altered insulin sensitivity means NAD+ can interfere with diabetes management and medications.
Antidepressants: Some antidepressants may affect NAD+ levels, potentially making the supplement less effective.

Lack of Long-Term Safety Data

Perhaps the most critical negative of NAD+ boosters is the lack of robust, long-term human safety studies. The current evidence largely stems from small, short-term trials (typically 6-20 weeks) that, while generally showing good tolerability, cannot rule out rare or long-term complications. Most long-term safety observations come from animal studies, which do not always translate to human outcomes. This gap in knowledge makes the long-term use of NAD+ supplementation a gamble for users.

NAD+ Supplementation vs. Natural Boosting Methods

To illustrate the differences in risk profiles, consider this comparison between boosting NAD+ via supplements versus natural lifestyle modifications.


Feature	NAD+ Supplements (e.g., NR, NMN)	Natural Methods (Exercise, Diet, Fasting)
Cost	Often expensive and ongoing	Minimal to no extra cost
Immediate Side Effects	Risk of nausea, headaches, flushing, GI issues	Very low risk of adverse side effects
Systemic Risks	Potential for liver strain, metabolic disruption, cancer interaction	Supports natural metabolic balance
Long-Term Safety	Limited data, effects of prolonged use are not well understood	Well-established long-term safety and benefits
Dosage Control	Difficult to pinpoint optimal dose; risk of over-supplementation	Body naturally regulates its own NAD+ production
Effectiveness	Shown to increase blood NAD+ levels, but clinical outcomes vary and need more research	Clinically proven to increase NAD+ and improve metabolic function

Conclusion: Navigating the Trade-Offs

Before rushing to embrace NAD+ supplements as a fountain of youth, it is crucial to understand the negatives of NAD+. While the potential benefits for cellular health and metabolism are promising, significant risks exist, including common side effects, interactions with cancer and medication, and potentially stressing the liver and pancreas at high doses. The biggest limitation is the lack of long-term human data, making a risk-benefit analysis challenging for extended use. Anyone considering NAD+ supplementation, especially those with underlying health conditions or on medication, should consult a healthcare provider. Often, safer and well-proven alternatives like regular exercise, a balanced diet, and intermittent fasting can also effectively boost NAD+ levels with far fewer risks.

For more in-depth scientific reviews on the topic, a systematic review published in Experimental Gerontology provides a detailed benefit/risk analysis of NAD+ therapy.

Frequently Asked Questions

The most common negatives include temporary side effects such as nausea, headaches, skin flushing (especially with niacin), fatigue, and gastrointestinal issues like diarrhea and abdominal discomfort.

There is no evidence that NAD+ supplementation causes cancer. However, the theoretical risk is that boosting NAD+ could provide energy for pre-existing cancer cells to grow and spread. This makes it crucial for anyone with a history or high risk of cancer to consult a doctor.

Yes, high doses of NAD+ precursors have been linked to elevated liver enzymes and potential liver toxicity in some studies. Individuals with pre-existing liver or kidney conditions are particularly vulnerable and should avoid these supplements without medical supervision.

Yes, NAD+ supplements can interact with medications for blood pressure, diabetes, and depression. For example, they may alter insulin sensitivity or cause dangerously low blood pressure when taken with blood pressure medication.

The long-term negatives are not yet fully understood due to a lack of long-term human safety trials. While short-term studies show good tolerability, the long-term effects on metabolism, cellular processes, and potential rare complications are still under investigation.

Specific groups who should avoid NAD+ supplements include pregnant or breastfeeding women, individuals with a history of cancer, those with liver or kidney disease, and people taking medications for blood pressure or diabetes.

IV therapy can cause more immediate and intense symptomatic side effects, such as nausea and flushing, due to the rapid absorption. While generally mild, risks like allergic reactions or infection at the injection site are also possible.

Yes, you can increase NAD+ levels through natural methods. Regular exercise, intermittent fasting, and consuming a diet rich in niacin (vitamin B3), found in foods like tuna, chicken, and mushrooms, are all effective strategies.