What are the dosing recommendations for Nicotinamide Adenine Dinucleotide (NAD) supplementation?

NAD+ Supplementation Dosing Guidelines

For NAD+ supplementation, enteral nutrition should provide 18-40 mg of niacin per day in 1500 kcal, while parenteral nutrition should provide at least 40 mg of niacin per day. 1, 2

Standard Dosing Recommendations

• The American College of Nutrition recommends daily niacin (NAD+ precursor) intake of 16 mg/day for adult males (>14 years) and 14 mg/day for adult females (>14 years) 1
• Higher recommendations exist for pregnant women (18 mg/day) and lactating women (16 mg/day) 1
• For enteral nutrition support, 18-40 mg of niacin per day in 1500 kcal is the recommended dose 2
• For parenteral nutrition, at least 40 mg of niacin per day should be provided 2

Safety and Upper Limits

• The upper intake limit for free nicotinic acid (a form of niacin) is set at 10 mg/day due to potential flushing effects 1, 2
• The upper intake limit for nicotinamide is approximately 900 mg/day for adults 1, 2
• Flushing, a common side effect of niacin supplementation, typically occurs within 30 minutes of ingestion and can happen at doses as low as 30 mg 3
• Serious hepatotoxicity can occur with niacin doses around 3 g per day 3

Therapeutic Dosing for Specific Conditions

• For treatment of traditional pellagra (niacin deficiency), nicotinic acid at 15-20 mg/day or nicotinamide at 300 mg/day is effective 3
• In mitochondrial myopathy patients, niacin doses of 750-1000 mg/day have been shown to increase blood NAD+ levels up to 8-fold and improve muscle strength 4
• For multiple acyl-CoA dehydrogenase deficiency (MADD) patients, higher doses of riboflavin (50-200 mg/day) may be needed as a cofactor 3

Administration Routes

• The oral/enteral route should be used whenever the gastrointestinal tract is functional 3
• In cases of malabsorption or short bowel syndrome, the parenteral route can be used 3
• For clinical riboflavin deficiency (which affects NAD+ metabolism), IV administration of 160 mg for four days may be necessary 3

Monitoring

• In case of clinical symptoms of deficiency (diarrhea, dermatitis, and dementia - classic pellagra), blood or tissue NAD levels may be measured 3
• If measurement is difficult to arrange, storing a blood sample and awaiting the effects of niacin supplements on symptoms may be a pragmatic alternative 3
• Urinary metabolites (N-methyl-nicotinamide and N-methyl-2-pyridone-carboxamide) can also be used to assess niacin status 1

Special Considerations

• Age-related decline in cellular NAD+ levels has been documented, and supplementation may help maintain NAD+ levels that decrease with age 1
• NAD+ precursors like nicotinamide riboside (NR) have been shown to increase NAD+ levels by approximately 40% at recommended doses and 90% at double doses compared to placebo 5
• Chronic supplementation with nicotinamide riboside has been found to be well-tolerated in healthy middle-aged and older adults 6
• Common side effects associated with NAD+ supplementation include muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches, though these generally do not present serious health risks 7

Dietary Sources

• Dietary sources of niacin include fortified packaged foods, meat and poultry, red fish such as tuna and salmon, and nuts, legumes, and seeds 1, 2
• Niacin can also be synthesized from the amino acid tryptophan in the liver (1 mg nicotinamide = 1 niacin equivalent) 3