What are the benefits of taking Nicotinamide adenine dinucleotide (NAD) supplements?

Why Take NAD+ Supplements

The primary reason to take NAD+ supplements is to restore age-related declines in cellular NAD+ levels, which may improve energy metabolism, support DNA repair, and potentially reduce cardiovascular risk factors, though you should use oral NAD+ precursors (niacin, nicotinamide riboside, or nicotinamide mononucleotide) rather than injectable forms. 1, 2, 3

Core Functions and Age-Related Decline

NAD+ serves as a coenzyme for over 400 enzymatic reactions in your body, making it essential for more biological processes than any other vitamin-derived coenzyme. 1 The key functions include:

• Energy metabolism: NAD+ plays a central role in converting nutrients into usable energy through mitochondrial function 1, 3
• DNA repair: Acts as a cofactor for poly (ADP-ribose) polymerases that repair oxidative DNA damage 3
• Cellular stress responses: Supports SIRT1 activity and other protective mechanisms 3
• Antioxidant effects: Helps manage reactive oxygen species production 1, 3

Cellular NAD+ levels decline significantly with age (correlation coefficient of -0.706 in men and -0.537 in women), which contributes to age-related physiological decline, increased oxidative stress, impaired mitochondrial function, and decreased ATP production. 3

Evidence-Based Benefits

Cardiovascular Effects

The most promising human evidence comes from a 2018 randomized, double-blind, placebo-controlled trial showing that nicotinamide riboside (NR) supplementation may reduce blood pressure and arterial stiffness in healthy middle-aged and older adults. 4 This represents the highest quality clinical evidence for NAD+ precursor supplementation.

General Health Parameters

A 2024 systematic review of 10 randomized clinical trials (489 participants total) found that NADH and NAD+ precursor supplementation was associated with: 5

• Decreased anxiety levels 5
• Reduced maximum heart rate after stress testing 5
• Increased muscle insulin sensitivity and improved insulin signaling 5
• Improved quality of life and sleep quality in chronic fatigue syndrome patients 5
• Reduced inflammatory cytokines in serum and cerebrospinal fluid 5

Cognitive Function

A 2024 trial in older adults with mild cognitive impairment showed NR was well-tolerated and safely increased blood NAD+ levels 2.6-fold, though cognitive measures remained stable rather than improved. 6 This suggests NAD+ supplementation may be more preventive than therapeutic for cognitive decline.

Recommended Approach to Supplementation

Start with Dietary Sources

Before considering supplements, optimize dietary niacin intake from: 1, 7

• Fortified packaged foods (highest content) 1
• Meat and poultry 1
• Red fish such as tuna and salmon 1
• Nuts, legumes, and seeds (lesser amounts) 1

Oral Supplementation Guidelines

If supplementing, use oral forms only—never injectable NAD+. 2 The established recommendations are:

Daily intake targets: 1, 7

• Adult males (>14 years): 16 mg/day 1
• Adult females (>14 years): 14 mg/day 1
• Pregnant women: 18 mg/day 1
• Lactating women: 16 mg/day 1

Upper safety limits differ by form: 1, 7

• Free nicotinic acid: 10 mg/day (causes flushing at higher doses) 1, 7
• Nicotinamide: approximately 900 mg/day for adults 1, 7
• Clinical doses for specific conditions can reach 3 g/day under medical supervision 1

Precursor Selection

Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are preferred over nicotinic acid because they effectively raise NAD+ levels without causing the flushing side effects common with nicotinic acid. 7, 4 NR has the strongest clinical trial evidence in humans. 4

Safety Profile and Side Effects

NAD+ precursor supplementation is generally well-tolerated with low incidence of side effects. 5 The most common adverse effects reported include: 5

• Muscle pain 5
• Nervous system symptoms 5
• Fatigue 5
• Sleep disturbance 5
• Headaches 5
• Gastrointestinal symptoms (nausea, vomiting, diarrhea with NMN) 7

None of these adverse events presented serious health risks in clinical trials. 5

Critical Warnings

Avoid Injectable NAD+

Injectable NAD+ is not FDA-approved, not recommended in any clinical practice guidelines, and poses significant safety risks including: 2

• Infection risk from improper sterile technique 2
• Potential hypersensitivity reactions 2
• Unknown pharmacokinetics when administered parenterally 2
• No standardized dosing protocols 2
• Falls outside standard medical practice 2

Potential Contraindications

NAD(P)H oxidase activity has been implicated in anthracycline-induced cardiotoxicity, raising theoretical concerns about NAD supplementation in patients receiving these chemotherapy agents. 2 Discuss with your oncologist if this applies to you.

Monitoring Considerations

If you want to assess niacin/NAD+ status, urinary metabolites can be measured: 1, 7

• N-methyl-nicotinamide (NMN) - most sensitive to marginal intake 1
• N-methyl-2-pyridone-carboxamide (2-Pyr) 1
• These can be quantified using HPLC with ultraviolet detection or HPLC-MS/MS 1

Blood NAD+ levels can also be measured directly if clinical symptoms suggest deficiency. 7

Bottom Line Algorithm

1. First: Optimize dietary niacin intake from whole foods 1, 7
2. If supplementing: Choose oral nicotinamide riboside (strongest human evidence) or nicotinamide (avoids flushing) 7, 4
3. Stay within safety limits: ≤900 mg/day for nicotinamide 1, 7
4. Never use injectable forms 2
5. Consider supplementation most strongly if: middle-aged or older with cardiovascular risk factors 4 or documented niacin deficiency 1
6. Monitor for common side effects: muscle pain, GI symptoms, sleep changes 5

Human trials are still limited, and while NAD+ precursors show promise for healthspan extension, the evidence is strongest for cardiovascular benefits rather than dramatic anti-aging effects. 4, 8, 5