MATERIALS AND METHODS
This narrative review considered all types of published journal
articles (clinical trials, case studies, scientific reviews). Studies
were identified by searching the PubMed database and
reference lists of respective articles. Only articles available in
English were considered for this review.
RESULTS
1: Increased NAD+ leads to KC chemoprevention.
NAM supplementation leads to decreased numbers of existing AKs, decreased development of new AKs, and decreased incidence of KC in high-risk skin cancer populations.1-3 This effect is likely due to a NAM-induced increase in NAD+ availability within keratinocytes.6,14 Animal models indicate that NAD+ deficiency increases cellular sensitivity to UV light, exhibits impaired ability to repair damaged DNA, and has increased genomic instability.14 Correlation work in humans suggest that NAD+ levels also decrease with aging, leading to the hypothesis that NAD+ depletion is causally related to aging and age-associated disease, including oncogenesis.4,5
2: NMN and NR supplementation more efficiently increase NAD+ levels than NAM supplementation, making them more promising treatments for age-associated disease related to NAD+ depletion.
Recent work has suggested that supplementation with NR and NMN may be a more effective means than NAM to increase cellular NAD+ levels. Mice treated with oral NMN vs NAM have increased tissue levels of NAD+.10,15 Humans and mice treated with oral NR vs NAM have, respectively, increased blood and hepatic levels of NAD+.13,16 These results may be due to both pharmacokinetics and pharmacodynamics; NR and NMN are more directly synthesized to NAD+ (Figure 1).13,17
Preliminary animal models have shown promising effects of treatment with NR and NMN; specifically, work suggests that NR and/or NMN can: 1) help treat numerous age-associated diseases (such as hepatic steatosis), 2) improve measurements of metabolic outcomes, 3) improve skeletal muscle mitochondrial function in vitro, 4) mitigate against acute kidney injury, and 5) protect against cardiac ischemia-reperfusion injury.10,15,18 Compared with untreated mice, NR-treated mice had longer lifespans, less cellular DNA damage, and improved mitochondrial and stem cell function.11 Similar results were found in yeast and C. elegans.19,20
3: NMN and NR are safe and well tolerated.
Like NAM, both NR and NMN molecules are water-soluble vitamin B3 derivatives endogenously present in human cells and food. NMN and NR supplementation has been used extensively in animals with no reported toxicity or serious adverse side effects to date.10,21 Over the past 2 years, several small trials of NMN and NR supplementation in humans have been published. One study used oral NMN supplementation in 25 pre-diabetic postmenopausal women at a dose of 250 mg / day and found that supplementation increased muscle insulin sensitivity without causing any adverse events.22 A second study looked at the effects of NMN supplementation on the aerobic capacity of runners; 36 participants were given either 300 mg/day (n=12), 600 mg/day (n=12), or 1200 mg/day (n=12) of NMN, and no side effects or adverse events were reported at any NMN dose.23 Several small trials have tested supplementation of NR at doses ranging from 300 to 2000 mg /day in adults without any reported adverse events.24,25 Although the United States (US) Food and Drug Administration regulating body has not yet approved either molecule for healthcare purposes, both NMN and NR supplements are easily available online as unregulated supplements, and many consumers are already taking them at doses ranging from 500 mg to 1000 mg/day, with no published data on adverse outcomes.
NAM supplementation leads to decreased numbers of existing AKs, decreased development of new AKs, and decreased incidence of KC in high-risk skin cancer populations.1-3 This effect is likely due to a NAM-induced increase in NAD+ availability within keratinocytes.6,14 Animal models indicate that NAD+ deficiency increases cellular sensitivity to UV light, exhibits impaired ability to repair damaged DNA, and has increased genomic instability.14 Correlation work in humans suggest that NAD+ levels also decrease with aging, leading to the hypothesis that NAD+ depletion is causally related to aging and age-associated disease, including oncogenesis.4,5
2: NMN and NR supplementation more efficiently increase NAD+ levels than NAM supplementation, making them more promising treatments for age-associated disease related to NAD+ depletion.
Recent work has suggested that supplementation with NR and NMN may be a more effective means than NAM to increase cellular NAD+ levels. Mice treated with oral NMN vs NAM have increased tissue levels of NAD+.10,15 Humans and mice treated with oral NR vs NAM have, respectively, increased blood and hepatic levels of NAD+.13,16 These results may be due to both pharmacokinetics and pharmacodynamics; NR and NMN are more directly synthesized to NAD+ (Figure 1).13,17
Preliminary animal models have shown promising effects of treatment with NR and NMN; specifically, work suggests that NR and/or NMN can: 1) help treat numerous age-associated diseases (such as hepatic steatosis), 2) improve measurements of metabolic outcomes, 3) improve skeletal muscle mitochondrial function in vitro, 4) mitigate against acute kidney injury, and 5) protect against cardiac ischemia-reperfusion injury.10,15,18 Compared with untreated mice, NR-treated mice had longer lifespans, less cellular DNA damage, and improved mitochondrial and stem cell function.11 Similar results were found in yeast and C. elegans.19,20
3: NMN and NR are safe and well tolerated.
Like NAM, both NR and NMN molecules are water-soluble vitamin B3 derivatives endogenously present in human cells and food. NMN and NR supplementation has been used extensively in animals with no reported toxicity or serious adverse side effects to date.10,21 Over the past 2 years, several small trials of NMN and NR supplementation in humans have been published. One study used oral NMN supplementation in 25 pre-diabetic postmenopausal women at a dose of 250 mg / day and found that supplementation increased muscle insulin sensitivity without causing any adverse events.22 A second study looked at the effects of NMN supplementation on the aerobic capacity of runners; 36 participants were given either 300 mg/day (n=12), 600 mg/day (n=12), or 1200 mg/day (n=12) of NMN, and no side effects or adverse events were reported at any NMN dose.23 Several small trials have tested supplementation of NR at doses ranging from 300 to 2000 mg /day in adults without any reported adverse events.24,25 Although the United States (US) Food and Drug Administration regulating body has not yet approved either molecule for healthcare purposes, both NMN and NR supplements are easily available online as unregulated supplements, and many consumers are already taking them at doses ranging from 500 mg to 1000 mg/day, with no published data on adverse outcomes.
DISCUSSION
NAM is an important chemopreventative molecule for KC,
thought to primarily act via increasing intracellular NAD+.
Recent in vivo work in humans and animals has shown that oral
supplementation of NR and NMN may increase NAD+ levels
