NAD+, or niacinamide adenine dinucleotide, is a derivative of niacin (Vitamin B3). It turns out to be critically important to a host of different physiological processes. Many of these processes relate directly to energy production, cellular repair, and anti-aging.
How NAD+ Relates to Other Forms of Vitamin B3
The two most physiologically useful forms of Vitamin B3, at least for the purposes we’re discussing in this article, are NAD+ and NADH. These are the oxidized and reduced forms of the same molecule, respectively.
Other forms include niacin or nicotinic acid (two names for the same molecule, if it weren’t confusing enough). This version is the one commonly used to lower lipid levels, and can cause “flushing” at high doses—unless in the extended release version that doesn’t hit the bloodstream all at once. The concern with this approach to lipid lowering is the potential for elevating liver enzymes, which increases with the no-flush form. Inositol hexaniacinate (or hexanicotinate) is niacin complexed with inositol, another way to avoid flushing.
Niacin can be converted into niacinamide (also called nicotinamide). Niacinamide can also be synthesized via the amino acid tryptophan. Niacinamide does not generally cause flushing, but also has little effect on lowering lipid levels. It is a closer precursor to NAD+/NADH than niacin, but there are some potential down sides to using it for this purpose, which we’ll discuss below. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are also versions of niacinamide (or nicotinamide).
It is possible to take reduced niacinamide adenine dinucleotide (NADH), which can convert into NAD+.
All of the previous forms of niacin can eventually be converted into NAD+ as well, though they’re not all created equal when it comes to NAD+ benefits.
NAD+, ATP Production, and Metabolism
The oxidized form of NAD+, NADH, is one of two primary electron carriers which enters the Electron Transport Chain (ETC) of the mitochondria, ultimately resulting in the production of ATP (the body’s primary energy currency). When NADH passes off its electron in the ETC, it becomes NAD+ again. So in a very direct way, NAD+/NADH is necessary for the energy production that drives the body’s metabolism. The body gets two benefits from this exchange: an increase in ATP, and an increase in NAD+.
The mitochondria are very efficient in this process. ATP is energy produced from food (starting from either glucose or fatty acids), but the body won’t produce more ATP than it can use. If too many electrons attempt to enter the electron transport chain at once (because we’re ingesting more calories than we can burn), they tend to leak out into the mitochondria. The other name for an unpaired electron is a free radical, which causes oxidative damage, leading to inflammation, mitochondrial damage, and potentially cell death when the damage becomes severe enough.
One of the best ways to prevent this process of mitochondrial damage is also one of the best ways to increase NAD+ production: calorie restriction. This means the mitochondria isn’t bombarded with electrons it can’t use.
Another great way to increase NAD+ involves the other side of the coin: using the calories you do have via exercise.
Even though the above approaches involve recycling the NAD+ already available, supplementation has been shown to increase NAD+ in the mitochondria directly. I suspect this is why niacin has been shown to be beneficial for lipid metabolism: it provides a key coenzyme necessary for turning fatty acids into energy.
NAD+/NADH can also be depleted by other metabolic processes besides ATP production, though.
NAD+ and PARPs (DNA Repair)
Enzymes called Poly(ADP-ribose) polymerase (PARPs for short) identify and tag damaged DNA for repair. But just like the mitochondrial engine requires fuel to work, so too does PARP. Its preferred energy source is also NAD+.
Not surprisingly, then, severe DNA damage can deplete available NAD+ by 20-30%. The longer we live, the more damage we accumulate from various toxins and oxidative stress. Since higher NAD+ is correlated with increased metabolic efficiency, this is one potential reason why metabolism declines with age.
NAD+ depletion for repair purposes potentially means more than just slowing down metabolism; it can also directly speed the aging process.
NAD+ and Sirtuins (Anti-Aging)
Silent Information Regulator Proteins, or sirtuins, manage a number of important cellular processes apparently connected to longevity.
Sirtuins also run on NAD+, so what boosts one, boosts the other. Sirtuin activity also is correlated with exercise, fasting, and caloric restriction. Because of this, higher sirtuin activity is therefore also inversely correlated with insulin resistance and obesity.
In other words, higher NAD+ appears to make you younger.
Of course, since increased PARP activity depletes NAD+, it will impair sirtuin activity as well. We already knew this intuitively: increased DNA and cellular damage speeds the aging process. This is just a more concise way to describe the mechanism behind it.
NAD+ Dietary Boosters
While the most efficient means of improving NAD+ levels is to avoid the toxicity that would trigger PARP activity in the first place, and to engage in regular exercise and caloric restriction, there are dietary and supplementary approaches to increasing NAD+ levels as well.
As mentioned above, the body can create NAD+ from the amino acid tryptophan, producing quinolinic acid as an intermediate. This isn’t very efficient, though. It takes on average around 60 mg tryptophan to make even 1 mg of niacin, so it’s kind of a last resort. The body only activates this pathway when NAD+ levels are quite low, relative to demand.
Due to feedback inhibition, niacinamide has been associated with sirtuin inhibition, though this is debatable. Until its relationship to sirtuins becomes clearer, it’s probably not the best choice for NAD+ supplementation. NADH has also been suggested as a sirtuin inhibitor for the same reason, though it appears that this only occurs at very high concentrations. This makes it still a reasonable choice for supplementation.
Nicotinamide riboside appears to be the most efficient supplementary form to convert into NAD+, surpassing nicotinamide mononucleotide. It also has been shown to enhance sirtuin activity, improving use of lipids for energy and protecting against diet-induced obesity. Unfortunately, it’s not cheap.
Baicalin, an extract of Chinese Skullcap/scutellaria baicalensis, also stimulates sirtuin activity, as does apigenin, an extract of chamomile.
More studies are needed to clarify the NAD+/PARP/Sirtuin relationship to aging, but the basic recommendations to increase your NAD+ levels are neither new nor surprising. It just gives you another reason to do what you knew you should be doing anyway.
- Engage in regular exercise, incorporating both strength training and cardio.
- Consider an occasional short fast, or intermittent fasting.
- Eat real food, and only as much as you need (perhaps a little bit less!)
- Decrease your EMF exposure where you can (a known mitochondrial toxin)
- Optimize your detox pathways.
- Make sure your multivitamin or your B vitamin has enough niacin to act as a precursor (15-25 mg is sufficient under normal conditions).
You can also consider supplementing with nicotinamide riboside or NADH, if you’ve already done the recommendations above. Quercetin, and a combo including baicalin and apigenin are also good options.