More on NAD+ Boosting Supplements

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• NAD+ boosting supplements carry risks, including potential exacerbation of infections, autoimmune issues, and tumor promotion, necessitating caution, especially for those with cancer or inflammatory disorders.  Copied to clipboard!
• Supplementation with NAD precursors like NR and NMN shows little clear evidence of human clinical benefit, possibly due to the complexity of NAD physiology and lack of funding for large trials.  Copied to clipboard!
• Natural methods like exercise significantly boost the key NAD-synthesizing enzyme NAMPT and increase muscle NAD levels, and consuming antioxidant/anti-inflammatory phytonutrients can conserve NAD by inhibiting NAD-guzzling enzymes like PARP1 and CD38.  Copied to clipboard!

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NAD+ Supplement Risks

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(00:00:17)

• Key Takeaway: NAD precursors like NR and NMN share concerns regarding surgery inhibition and methyl depletion due to raising NAM levels.
• Summary: Reported side effects for NAD precursors are generally minor, but theoretical concerns include exacerbation of infections by Haemophilus bacteria, which rely on host NAD levels. Elevated NAD may also fuel immune system overreaction in autoimmune and inflammatory diseases. NAMPT, the primary NAD synthesizing enzyme, is elevated in inflamed tissues, suggesting NAD boosting could negatively impact chronic autoimmune conditions.

Supplement Efficacy and Limitations

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(00:04:29)

• Key Takeaway: No NAD-boosting supplement is a clear standout, as preclinical effects have rarely translated into proven human clinical benefit.
• Summary: It is too early to confirm if NAD booster supplementation will meet the hype, requiring more extensive, long-term studies for safety and efficacy. Funding for these trials is scarce because NAD precursors cannot be patented as natural products. The body may resist blunt supplementation, suggesting natural approaches might be superior.

Natural NAD Boosting Strategies

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(00:05:48)

• Key Takeaway: The body can increase NAD levels through three main ways: increasing precursors, activating synthesizing enzymes like NAMPT, or inhibiting degradation.
• Summary: NAMPT expression declines significantly with age in human muscle and liver, and this decline is exacerbated by age-related diseases. Boosting NAMPT increases lifespan and aerobic capacity in rodents, comparable to dietary precursors. Exercise is a natural way to boost NAMPT; sedentary men and women showed a 127% increase in NAMPT levels after three weeks of stationary biking.

Conserving NAD Levels

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(00:08:18)

• Key Takeaway: Oxidative stress and inflammation cause NAD depletion by overactivating NAD-consuming enzymes PARP1 and CD38.
• Summary: PARP1 uses NAD to repair DNA damage, and accumulating damage with age drains NAD levels; preventing oxidative stress, such as avoiding high-fat diets, can restore NAD. CD38 activity rises with age due to chronic inflammation (inflammaging), and blocking it raises NAD levels in old mice. Antioxidant and anti-inflammatory phytonutrients found in plant foods are effective CD38 inhibitors.

Dietary Flavonoids as Inhibitors

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(00:12:24)

• Key Takeaway: Many flavonoids, such as cyanidin, quercetin, and apigenin, effectively inhibit CD38 and PARP1, conserving NAD levels.
• Summary: Cyanidin (red cabbage, blackberries) and quercetin (onions) were highly effective CD38 inhibitors in testing. Apigenin, found in parsley and chamomile tea, boosts NAD levels in mice by about 50%, equivalent to the maximum tolerable dose of NR. Dietary intake of proanthocyanidins (found in one apple) can boost NAD-conserving sirtuin activity in humans.