How To Boost NAD Levels To Fight Inflammation, Improve Recovery, and Slow Aging

Dr. Brener emphasizes that NR's anti-inflammatory benefits are now a 'proven fact,' supported by eight randomized clinical trials. He recounts how this benefit was often discovered as a secondary outcome in trials initially designed for other endpoints, such as improving grip strength. However, dedicated trials, like one involving COPD patients, confirmed NR's ability to reduce inflammatory markers. The mechanism is believed to involve rebuilding NAD supplies in systems under inflammatory attack, which helps detoxify free radical species and supports repair processes. This makes NR a potentially broadly useful supplement for combating 'inflammaging' and other inflammation-driven conditions.

Dr. Brener acknowledges that while rigorous placebo-controlled data on NR for exercise recovery is still emerging, there's strong anecdotal support from the sports world. He mentions that professional athletic programs, including the New England Patriots during Tom Brady's tenure, have used Niagen (a brand of NR) specifically for recovery. The rationale is that NAD is crucial for cellular repair, and exercise itself upregulates enzymes involved in NAD synthesis. Supplementing with NR is hypothesized to synergize with these natural adaptive responses, potentially enhancing the body's ability to recover from strenuous activity. He suggests that this is a promising area for future laboratory exercise physiology studies.

Dr. Brener suggests that NR could be a valuable tool for individuals experiencing circadian rhythm disruption, such as shift workers or those with jet lag. He explains that the NAD system is intricately linked to chronobiology, with many time-of-day cues influencing NAD synthesis and NAD-dependent metabolic processes. Pre-clinical mouse studies have shown that older mice losing their chrono-synchrony also exhibit disturbed NAD systems. Therefore, supplementing with NR, particularly in the morning (or at the start of a night shift worker's 'day'), could help support the NAD system during periods of misalignment. He recommends combining this with other established strategies like bright sunlight exposure at the appropriate time.

Dr. Brener highlights that obesity is a significant stressor on the NAD system. His lab's mouse experiments from 2016 showed that overfeeding mice a high-fat diet, pushing them into type 2 diabetes, disturbed their liver NAD system. Specifically, the pH (presumably referring to a pathway or enzyme related to NAD metabolism) was central to this disturbance, impairing the liver's ability to detoxify reactive oxygen species. He emphasizes that for individuals with overweight or obesity, addressing this through lifestyle changes or medical options (like GLP-1 medications in conjunction with resistance training) is a primary way to support NAD health, as it tackles a root cause of NAD system stress.

Dr. Brener strongly advocates for exercise as a fundamental way to support NAD levels. He cites clinical evidence, including a recent publication with a German group, showing that exercise increases the gene expression of NAD biosynthetic enzymes. This means that physical activity directly stimulates the body's machinery for making NAD. He also links exercise to mitochondrial biogenesis, a process where new mitochondria are formed, which he describes as 'rejuvenating.' The overarching message is that any form of exercise is beneficial, as it triggers a cascade of transcriptional pathways that support NAD and overall cellular health.

Dr. Brener clarifies that while the idea of NAD decline with age is prevalent, particularly on platforms like Instagram, direct evidence for a universal decline in human blood NAD levels is lacking. He notes that his lab's metabolomic analyses of human blood typically show consistent NAD+ levels (around 20 micromolar) in normal individuals, regardless of age. However, he acknowledges that NAD levels in specific tissues are likely disturbed or decline with age, and certain disease states, like mitochondrial disease or alcoholism affecting the liver, do show lower NAD levels in affected tissues or blood. The key distinction is that a systemic blood NAD decline in healthy aging humans is not as clearly evidenced as often portrayed.

Dr. Brener emphasizes that inflammatory processes are likely a major factor in disturbing the NAD system across many disease conditions. He cites his lab's 2020 research during the COVID-19 pandemic, where they found that coronavirus infection transcriptionally activated five members of the PARP superfamily. These PARPs consume NAD, leading to a depletion of NAD resources. This response is not unique to COVID but is a common innate immune reaction to invaders like double-stranded RNA, which the body recognizes as foreign. Therefore, chronic inflammation, whether from infection, obesity, or other stressors, can significantly tax the NAD system by upregulating NAD-consuming enzymes.

Dr. Brener highlights that while early clinical trials for NR sometimes missed their primary endpoints (e.g., improving grip strength in older men without exercise), subsequent analyses consistently revealed a strong anti-inflammatory effect. He notes that eight randomized clinical trials now demonstrate NR's ability to lower inflammatory markers such as IL-6 and IL-10 in humans. One particularly compelling study, where anti-inflammation was the primary endpoint, involved patients with COPD, a highly inflammatory respiratory condition. In this trial, NR significantly reduced inflammatory markers in sputum, confirming its anti-inflammatory action in a disease-relevant context. This suggests that NR helps by rebuilding NAD supplies in systems under inflammatory attack, thereby aiding in the detoxification of free radical species and supporting repair processes.

Dr. Brener explains that the fundamental difference between NMN and NR lies in their ability to enter cells. Molecules with phosphate groups, like NAD and NMN, generally cannot cross cell membranes. Therefore, when NMN is taken orally, it must first be broken down into NR before it can be transported into cells. Once inside the cell, NR is then converted back into NMN and subsequently into NAD. This means that taking NMN orally essentially delivers NR to the cells, making NR a more direct and efficient precursor. He also raises concerns about the purity and label claims of many commercially available NMN products, noting that many do not contain the advertised amount of NMN or are contaminated.