Nutrition's Role: Does NAD+ Help with Fatigue?

November 9, 2025 •

5 min read

By age 50, human NAD+ levels may have dropped to half of what they were in our 20s. This significant decline in the essential coenzyme may impact cellular health and energy production, raising the question: Does NAD+ help with fatigue?

Quick Summary

NAD+ is a coenzyme crucial for energy metabolism and DNA repair. Levels naturally decline with age and stress, potentially causing cellular dysfunction and fatigue. While evidence is still emerging, replenishing NAD+ through diet, supplements, or lifestyle changes may support mitochondrial function and enhance energy, offering a potential strategy for chronic tiredness.

Key Points

NAD+ is a Key Energy Coenzyme: As an essential coenzyme, NAD+ is required for hundreds of metabolic reactions, most notably for converting food into cellular energy (ATP) within the mitochondria.
Low NAD+ Linked to Fatigue: The natural decline of NAD+ with age, stress, and poor lifestyle habits is associated with reduced mitochondrial function, leading to symptoms like fatigue and 'brain fog'.
Multiple Ways to Boost NAD+: Levels can be increased through diet (B3 vitamins, tryptophan), supplements (NR, NMN), intravenous therapy, exercise, and intermittent fasting.
Evidence is Emerging, Not Conclusive: While preclinical studies and testimonials show promise, particularly for chronic fatigue syndrome (CFS), large-scale human clinical trials are still limited, and individual results can vary.
Consider Safety and Side Effects: Potential side effects are mostly mild, but individuals with pre-existing conditions, especially a history of cancer, should consult a doctor before starting supplementation.
Holistic Approach is Best: Combining NAD+ support with a balanced diet, regular exercise, and other healthy lifestyle choices is the most effective and sustainable strategy for maintaining energy levels.

Understanding the Fundamental Role of NAD+

Nicotinamide adenine dinucleotide, or NAD+, is a vital coenzyme found in every cell of the body. It exists in two primary forms: the oxidized form, NAD+, and the reduced form, NADH. This molecule is fundamental to cellular metabolism, playing a pivotal role in converting the food we eat into usable energy for our cells. Its function is so critical that a sufficient supply is essential for the body's overall health and vitality.

How NAD+ Fuels Your Cells

Inside the body's cells, tiny organelles called mitochondria are responsible for producing over 90% of the body's energy. NAD+ is a key player in this process, specifically in the electron transport chain, where it carries electrons to generate adenosine triphosphate (ATP), the body's main energy currency. When NAD+ levels are optimal, this process runs efficiently, and our cells have the fuel they need for everything from muscle contraction to brain activity.

The Connection Between Low NAD+ and Fatigue

As we age, NAD+ levels naturally decline. Stress, poor diet, and a sedentary lifestyle can accelerate this depletion. This gradual decrease in NAD+ can impair mitochondrial function, leading to less efficient ATP production. The result is often physical tiredness and mental sluggishness, symptoms commonly associated with low energy.

Furthermore, NAD+ is crucial for activating sirtuins, a class of proteins that regulate cellular health, including DNA repair. When NAD+ is low, sirtuin activity decreases, and cellular maintenance processes suffer, contributing to cellular stress and further exacerbating feelings of fatigue. This link is particularly relevant for conditions like Chronic Fatigue Syndrome (CFS), where mitochondrial dysfunction is a common feature.

Strategies to Support NAD+ Levels

For those looking to combat fatigue, there are several avenues to explore for boosting NAD+ levels. These range from dietary adjustments to supplements and lifestyle changes.

Nutritional Strategies for Boosting NAD+

While you cannot get NAD+ directly from food, you can consume foods rich in its precursors, such as vitamin B3 and tryptophan.

Foods rich in Vitamin B3 (Niacin/Nicotinamide): Include poultry, fish (like tuna and salmon), mushrooms, whole grains, and fortified foods.
Foods with Tryptophan: This amino acid can be converted into NAD+ through a different metabolic pathway. Sources include poultry, eggs, and dairy.
Cruciferous Vegetables: Broccoli, for example, provides precursors like sulforaphane that support mitochondrial health.
Fermented Foods: Items like nutritional yeast and kefir contain NAD+ precursors and support gut health, which is linked to metabolism and inflammation.

Supplements and Therapies

To achieve higher, more concentrated doses of NAD+ precursors, many turn to supplements or direct therapies.

Oral Supplements: The most popular precursors are Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN). These are generally well-tolerated and can increase NAD+ levels over time.
NAD+ IV Therapy: Intravenous infusions deliver NAD+ directly into the bloodstream, bypassing the digestive system for more immediate absorption. This is often used for targeted interventions.

Comparison of NAD+ Boosting Methods


Method	How It Works	Speed of Effect	Best For	Side Effects/Considerations
Diet	Provides precursors (B3, Tryptophan) for the body's natural synthesis pathways.	Slow, gradual	Long-term maintenance, foundational health.	Safe; may not provide high enough levels for significant boost.
Oral Supplements (NR/NMN)	Provides higher, concentrated doses of direct precursors.	Moderate, cumulative effect over weeks to months.	Consistent, daily support to combat age-related decline.	Generally mild side effects; dosage variability.
IV Infusion	Administers NAD+ directly into the bloodstream.	Rapid, immediate effects reported.	Targeted interventions, quick energy boost.	Potential nausea, bruising, cost, and requires medical supervision.
Exercise	Increases energy demand, stimulating NAD+ production and mitochondrial function.	Gradual, depends on frequency and intensity.	Natural and synergistic with other methods.	Low risk, part of a healthy lifestyle.
Intermittent Fasting	Triggers cellular repair mechanisms, promoting NAD+ production.	Varies, depends on fasting schedule.	Promoting cellular health and longevity.	Not for everyone; consult a doctor before starting.

Scientific Evidence and Considerations for Fatigue

Research has provided promising, though still emerging, evidence for NAD+ therapy in addressing fatigue, particularly in specific conditions. Mitochondrial dysfunction is a core feature in Chronic Fatigue Syndrome (CFS), and NAD+ therapy is being investigated as a way to address this root cause. Some studies and clinical observations suggest benefits for energy levels, mental clarity, and overall well-being in CFS patients.

A 12-week placebo-controlled study with CFS patients using NADH (20mg/day) along with CoQ10 showed significant reductions in perceived cognitive and overall fatigue. However, the overall body of clinical evidence is still limited, with some trials showing no effect on energy expenditure in certain populations despite increased NAD+ levels. This highlights that NAD+ is not a magic bullet and responses can vary significantly. More large-scale, controlled trials are needed to fully establish efficacy and identify which patient populations benefit most.

Potential Side Effects and Safety Precautions

While NAD+ supplements and therapies are generally well-tolerated, it is crucial to be aware of potential side effects and safety considerations.

Mild side effects: Some individuals may experience temporary nausea, bloating, headaches, or flushing (with higher doses of niacin-based precursors).
Interactions: Caution is advised for those on medications for blood sugar regulation, blood thinners, or antidepressants, as NAD+ can influence their effects.
Cancer Concerns: Because NAD+ supports cellular growth, individuals with a history of cancer should use caution and consult their doctor before taking supplements, as it could theoretically support the growth of cancer cells.
Medical Supervision: Consulting a healthcare professional is essential before starting any new supplementation regimen, especially for those with pre-existing conditions or those on other medications.

Conclusion: Navigating the Role of NAD+ in Fighting Fatigue

In summary, the science behind NAD+ and its potential role in mitigating fatigue is compelling, especially given its central function in cellular energy production. The age-related decline of NAD+ levels is a confirmed phenomenon, and restoring these levels through diet, lifestyle, and supplementation offers a promising avenue for improving cellular function and combating tiredness. While anecdotal evidence and initial studies, particularly in the context of chronic fatigue syndrome, suggest positive outcomes, it is important to maintain realistic expectations. NAD+ is not a guaranteed cure, and individual responses vary. Adopting a holistic approach that includes a nutrient-dense diet and healthy lifestyle habits remains the foundation of robust energy levels. Supplementation can be a supportive measure, but should always be pursued with professional medical guidance to ensure safety and effectiveness.

For more detailed research, explore scientific literature, such as the review on NAD+ metabolism in Nature.

Frequently Asked Questions

NAD+ is a coenzyme in every cell that helps convert food into cellular energy, or ATP, particularly within the mitochondria. Without enough NAD+, this energy-making process slows down, potentially leading to fatigue.

There is no cure for CFS, and NAD+ is not guaranteed to be a cure. However, because CFS is linked to mitochondrial dysfunction and low NAD+ levels, some studies and patient reports indicate that NAD+ supplementation may help improve symptoms of fatigue, though more research is needed.

The most common and well-studied oral precursors are Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN). Niacin (Vitamin B3) and tryptophan can also support NAD+ synthesis through other pathways.

Foods containing NAD+ precursors include poultry, fish, whole grains, and legumes. Good sources of Vitamin B3 (niacin) are mushrooms, chicken breast, and beef. Tryptophan-rich foods like eggs and milk also support production.

Common side effects are generally mild and may include flushing (with niacin), nausea, and headaches. More serious reactions are rare but possible. Individuals with pre-existing conditions or on certain medications should consult a doctor.

Oral supplements like NR and NMN are convenient for daily support, but may take longer to show effects. IV infusions deliver NAD+ directly into the bloodstream, which may produce faster, more potent results, though they are more expensive and require medical supervision.

Since NAD+ levels decline with age, and this decline is linked to age-related energy reduction, restoring NAD+ is proposed as a way to combat age-related fatigue. Some research in animal models and clinical observations support this, but further human trials are necessary.

Individuals with a history of cancer, metabolic disorders, or liver conditions, as well as those on medications for blood sugar or blood thinners, should consult a healthcare provider before taking NAD+ supplements.