What are the guidelines for NAD+ (Nicotinamide adenine dinucleotide) supplementation?

Guidelines for NAD+ (Nicotinamide Adenine Dinucleotide) Supplementation

There are no established clinical guidelines specifically for NAD+ supplementation beyond the recommended dietary allowances for niacin (vitamin B3), which is a precursor to NAD+. 1

Recommended Dietary Intake of Niacin (NAD+ Precursor)

• Daily Recommended Intake (DRI) for niacin varies by age and sex:

  • 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

• Parenteral nutrition dosing: 40 mg/day of niacin 1

Upper Intake Levels and Safety

• Nicotinic acid (a form of niacin):

  • Upper Limit (UL): 10 mg/day for free nicotinic acid 1
  • This limit is derived from flushing effects seen at 30 mg/day in young subjects 1
  • Clinical doses for hypercholesterolemia treatment can be much higher (3 g/day) 1

• Nicotinamide (another form of niacin):

  • Upper Limit (UL): 12.5 mg/kg body weight/day or approximately 900 mg/day for adults 1, 2
  • No adverse effects observed at doses up to 25 mg/kg body weight/day in diabetic subjects 1
  • Unlike nicotinic acid, nicotinamide does not cause flushing 2

Common Side Effects of NAD+ Supplementation

• Potential side effects of NAD+ precursor supplementation may include:
  • Gastrointestinal symptoms (nausea, vomiting, diarrhea) 2, 3
  • Muscle pain 3
  • Nervous disorders 3
  • Fatigue 3
  • Sleep disturbance 3
  • Headaches 3

Clinical Evidence and Applications

• NAD+ is involved in over 400 enzymatic reactions in the body 1, 2

• Functions include:

  • Energy metabolism and ATP production 2, 4
  • DNA repair 2, 3
  • Gene expression regulation 2, 3
  • Stress response mechanisms 2

• Recent clinical trials have shown:

  • NAD+ precursor supplementation is generally safe and well-tolerated 3, 5
  • Some studies report improvements in quality of life measures 3
  • Modest effects observed in people with obesity 6
  • Potential benefits for muscle insulin sensitivity 3

Considerations for Specific Populations

• Aging populations:

  • Age-related decline in cellular NAD+ levels has been documented 1, 5
  • Supplementation may help maintain NAD+ levels that decrease with age 5

• Patients with metabolic disorders:

  • NAD+ precursors have shown benefits in preclinical models of non-alcoholic fatty liver disease (NAFLD) 6
  • Clinical translation has shown more modest effects than preclinical studies 6

• Cardiovascular conditions:

  • Preclinical evidence suggests potential benefits in heart failure, ischemic-reperfusion injury, and arrhythmias 7
  • Clinical evidence remains limited 7, 5

Practical Recommendations

• Dietary sources of niacin (NAD+ precursor) include:

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

• NAD+ precursor supplements (nicotinamide riboside, nicotinamide mononucleotide) are available over-the-counter 6, 5

• Current research limitations:

  • Varying dosing regimens across studies 5
  • Small sample sizes in many clinical trials 5
  • Limited long-term safety data 5

Monitoring

• No standardized monitoring protocols exist specifically for NAD+ supplementation 1
• Urinary metabolites (N-methyl-nicotinamide and N-methyl-2-pyridone-carboxamide) can be used to assess niacin status 1