Spotlight on NAD+(nicotinamide adenine dinucleotide)
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells. It plays a crucial role in many cellular functions (over 300!), particularly in energy production and redox reactions (chemical reactions that involve the transfer of electrons).
NAD+ is most well-known for its role in energy production or cellular respiration, the process by which cells convert nutrients into energy. During the breakdown of glucose in cellular respiration, NAD+ accepts electrons and hydrogen ions, becoming reduced to NADH. NADH then carries these electrons and hydrogen ions to the electron transport chain, where they are ultimately used to generate ATP (adenosine triphosphate), the primary energy currency of cells.
NAD+ also plays a role in cellular maintenance and repair, cellular signaling and gene expression. It serves as a substrate for enzymes called sirtuins, which regulate various cellular processes, including DNA repair, cell cycle progression, and stress response. NAD+ acts as a signaling molecule in the cell where it tells the cell to switch on and off maintenance and repair pathways such as DNA repair enzymes--to make sure our cells stay in good health. The main reason why NAD+ can seem to regulate all these different functions is that it works in tandem with a group of proteins known as the sirtuins. Some people may have heard them referred to as “longevity proteins.” This is because these sirtuins are known to switch on a whole host of downstream pathways and processes that are beneficial for cellular health, that switch on recycling, switch on repair, switch on DNA repair. The link with NAD+ is that they are absolutely critically dependent on NAD+. NAD+ acts as a fuel to power the sirtuins. Sirtuins require NAD+ as a cofactor to carry out their enzymatic functions. Without NAD+, they don’t work.
As a general rule of thumb, if you have high levels of NAD+, you likely have good levels of energy production and good levels of cellular maintenance and repair. If you have low NAD+, energy can go down, and cellular maintenance and repair won’t be as effective.
Sadly, NAD+ levels decline naturally as we age. NAD+ has been estimated to drop by about 50% every 20 years starting from birth. Even by the time you’re 20, NAD+ drops by half. Then this level halves again. Then that level halves again. By the time we reach a more advanced age, NAD+ has dropped significantly, which can contribute to various chronic illnesses of aging.
A the same time NAD+ levels are dropping, demand for NAD+ in older cells goes up. This causes a lot of other downstream effects because what happens is, for example, we have a lot of inflammatory processes in older cells. There’s a really famous one called CD38. It’s an enzyme that seems to become upregulated with chronic low-grade inflammation as we get older. And CD38 just eats up NAD+. When it uses NAD+, it gets broken down. This is broken down in nicotinamide. Now in young cells, this nicotinamide would just be flipped straight back into NAD+ again via the salvage pathway. But, we know that enzyme isn’t working as efficiently. Therefore, what happens in the cells is that older cells start to build up this nicotinamide because it’s not getting recycled. Then the cells are like, “Oh my goodness, we need to maintain homeostasis. We don’t like it when things build up. How do we get rid of it?” What it does is it increases expression of another enzyme called NNMT, which is a key methylation enzyme. This enzyme sticks a methyl group on nicotinamide to signal its excretion from the cell. Then what you see is then further dysregulation because you start getting methyl donor depletion because it’s all being used up trying to get rid of this nicotinamide. Then you don’t have the methyl groups to be involved in other critical processes like epigenetics.
You can quickly see in older cells how you’ve got lack of recycling, you’ve got increased demand for NAD+, you’ve got inflammatory processes using the NAD+. Suddenly, everything’s going out of whack and one negative thing leads to another. Then it’s like the perfect storm for major NAD+ depletion.
But it’s not all doom and gloom, there are a number of ways we can act to boost NAD+ as we age.
There are several ways to increase NAD+ levels in the body:
1. NAD+ Precursors: NAD+ precursors are compounds that can be converted into NAD+ within the body. The two primary NAD+ precursors are nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). These precursors are readily available as dietary supplements and have been shown to effectively raise NAD+ levels in various tissues when consumed orally. NMN is the preferred way to go. 1 gram daily has been recommended. Resveratrol (1 gram daily) along with a fatty meal along with NMN has been shown to increase NAD+ levels.
2. Dietary Sources: building blocks for NAD+ can be obtained from dietary sources that contain niacin (vitamin B3). Foods rich in niacin include meat, fish, poultry, legumes, whole grains, and nuts. Consuming a balanced diet that includes these niacin-containing foods can help maintain adequate NAD+ levels.
3. Caloric Restriction and Fasting: Caloric restriction and intermittent fasting have been shown to increase NAD+ levels in animal studies. These practices reduce overall energy intake or alternate between periods of fasting and feeding, which can enhance NAD+ synthesis and promote its availability for cellular functions.
4. Exercise: Regular physical exercise has been linked to increased NAD+ levels. Studies have shown that exercise can upregulate NAD+ biosynthesis pathways and enhance the activity of NAD+-dependent enzymes. Aerobic exercise, high intensity interval training, weight lifting and resistance training exercises have all demonstrated the ability to boost NAD+ levels in skeletal muscle.
5. NAD+ Infusions: Intravenous infusion of NAD+ is a more direct method of increasing NAD+ levels. This approach involves delivering NAD+ directly into the bloodstream, bypassing the need for synthesis from precursors. NAD+ infusions are typically administered under medical supervision and may be used in specific clinical settings.
6. Cold & Heat Exposure can also stimulate production of NAD+.
It's important to note that while NAD+ precursors and other strategies can increase NAD+ levels, the extent of their effectiveness and their potential long-term effects on health are still being researched. If you're considering using NAD+ precursors or other approaches, it's advisable to consult with a functional medicine professional to discuss potential benefits, risks, and proper dosages based on your individual circumstances.
Your genes aren’t your destiny
“80% of our health in old age is due to our lifestyle and how we live; only 20% is genetic” – David Sinclair
Shade C. The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integr Med (Encinitas). 2020 Feb;19(1):12-14. PMID: 32549859; PMCID: PMC7238909.
