science
NAD supplements have received a lot of attention recently, often promoted as good for healthy aging, cognition, and metabolic wellness. But the evidence for these claims is fairly limited.
So what is NAD, and what health benefits does it actually offer? In this article, we’ll explore the science behind the nutrient, its possible benefits, different types of NAD supplements, and what you need to know if you want to consider taking NAD+.
NAD stands for nicotinamide adenine dinucleotide. In the body, it’s made from niacin (vitamin B3) and its derivatives, including:
Niacin has many pathways that it can be diverted to in the body, so you can’t control how much NAD is made from food sources alone. NAD is a molecule that can be formulated as a dietary supplement, so that it can be consumed without relying on the body to convert it.
While a lot is known about niacin, there is very little evidence from human clinical studies about NAD. Benefits need to be understood within that context. Animal research has shown promising results, but animal study results don’t necessarily translate into viable human health benefits. Here’s what we do know about the possible benefits:
Healthy cognitive function is of interest to many people, whether they’re concerned with healthy aging, optimal mental performance, good memory, and more. NAD+ precursors have been an interest of researchers in neurology, cognition, and metabolic fields. However, most current studies are from animal models, and even those findings range from positive to null to adverse. Well-designed human clinical trials are needed.
In one randomized, double-blind study of 207 people with a fatigue condition, participants received either placebo or a supplement that combined 20 mg of NADH (a reduced form of NAD) with 200 mg of coenzyme Q10. After 12 weeks, the group who received the supplements had a significant reduction in cognitive fatigue and improvements in quality of life, sleep duration and sleep efficiency. Larger studies are needed, but the results of this combination of supplements demonstrated promising potential for healthy brain energy support.
NAD has been studied for how it could impact metabolism and energy use in the body. In a 10-week randomized, double-blind trial, nicotinamide mononucleotide (NMN) was compared to placebo. NMN is a form of niacin that affects how the body chooses to convert it into niacin derivatives, including NAD. The study included 25 postmenopausal people who had metabolic factors and higher body weight. Those who took the NMN had better energy distribution after food intake, and improved muscular insulin communication. The placebo group showed no differences. In the group who took the NMN, NAD+ increased in the body, but did not continue to rise after 10 weeks when an additional single amount was given. No adverse effects were noted.
Another study of 140 healthy people with higher body weight compared nicotinamide riboside (NR), a precursor to NAD+, to a placebo condition. NR did not cause any serious adverse effects, with the most common side effects being mild nausea and muscle soreness. No flushing events were noted. The supplementation led to increases in blood levels of NAD+ in a dose dependent way after daily intake for 2 weeks: 100 mg of NR increased NAD+ by 22%, 300 mg of NR increased NAD+ by 51%, and 1,000 mg of NR increased NAD+ by 142%. Body weight parameters did not change between groups, and the researchers noted that the study was limited by a lack of diversity in the group participants. Another limitation is that the study was funded by the supplement manufacturer, and some company employees were also part of the research team. Additionally, larger studies are needed.
Another 6-week study looked at the effect of 1,000 mg per day of NR on mitochondrial energy, carbohydrate use, and other metabolic parameters in 13 people who had higher body weights. NR increased NAD+ in the supplement group but there were no changes in the placebo group. The NR group also had a slight increase in fat-free body mass compared to the placebo group, and experienced better skeletal muscle energy. NR supplementation did not impact mitochondrial energy or how the body used food for energy.
Overall, precursors to NAD can increase it in the body, but there are not yet consistent outcomes for weight or body composition when the body has higher NAD levels. More research is needed.
NAD+ (in its oxidized form) supports redox reactions in the body, which is how its function as a coenzyme is vital. Energy metabolism relies on numerous complex, rapidfire enzyme conversions and responses.
A study of 12 older people compared 1,000 mg of NR to placebo in a 21-day randomized, double-blind trial. NR increased NAD+ in the muscles and demonstrated some positive impacts on immune cell function and mitochondrial energy production and efficiency.
The data from this research is promising, but larger clinical trials need to be done before it’s clear whether these are repeatable benefits.
NAD+ supports enzymatic activity that has a direct impact on immune cellular function, metabolic signaling, and energy generation. Each of these are essential for healthy aging. The natural decline in enzymatic responses is part of what contributes to the process of aging.
Cell research, animal studies, and human trials have shown that NAD+ goes through a gradual, steady decline with advancing age. Because of this, research on NAD+ has been a prominent focus among scientists who study aging, health conditions, cognition, muscle maintenance, and more. But there’s still much to be learned, and in a lot of cases, there are more questions than answers about the mechanisms behind NAD+ and whether directly supplementing with NAD+ has the same potential that the naturally converted form does.
Most of the studies on NAD and healthy aging have only been done in test tubes or animals, so we really don’t know how it can affect human aging. The few studies that have involved niacin derivatives like NAD+ have been very small, many of them involving the brain or nervous system in some way.
More research needs to be done on supplementation with NAD directly. Larger, diverse groups of participants are also needed in clinical trials to extract meaningful conclusions about how NAD supplementation may affect aging.
Niacin is a nutrient in the B vitamin family that plays a role in cellular energy, ATP generation (the main way that cells get energy to perform functions), DNA integrity, cellular antioxidant defenses, and much more.
Niacin derivatives like NR and NMN can be converted into NAD in the body. NAD can be found in two forms, which have different actions in the body. NAD+ can be converted to NADH, and NADH can be converted into NAC+. They have different roles that are not interchangeable, but they are both essential.
NAD+ has a wide range of biological processes, influencing everything from genetic maintenance to energy production in cells It’s needed for more than 500 enzyme reactions in the body. NADH is needed for ATP generation and cellular energy.
While NAD+ levels naturally decline as part of aging, NADH levels naturally rise, though a balanced ratio between the two are important.
There are a few ways to get nicotinamide adenine dinucleotide from dietary supplements, though none of them are direct.
NAD+ provides the least direct way to actually increase your NAD levels because it degrades easily in supplement form. Also, once it enters the digestive system, NAD+ is converted into nicotinamide, and is not able to enter cells in its NAD+ state.
Niacin (also called nicotinic acid) can increase NAD in the body through a 3-step conversion. However, nicotinic acid can cause a common side effect known as the “niacin flush,” and may be uncomfortable.
Niacinamide, also called nicotinamide, is a precursor of NAD, too. This form does not cause skin flushing side effects like nicotinic acid.
Nicotinamide mononucleotide can be a precursor to NAD, but is not a direct form of vitamin B3. It has also been studied less than other precursors, and is less efficient than other options at converting to NAD.
Nicotinamide riboside is another form of vitamin B3 and is also a NAD precursor that does not cause flushing.
Supplements that increase NAD+ may result in no adverse effect or potentially lead to the below.
Most research on supplements that increase NAD, especially NR and NMN, have been done in animals. Long-term data is not available for these supplements, so safety profiles are largely unknown. It’s important to work with your medical provider before taking supplements, especially newer forms that have less robust research behind them.
With a limited number of human clinical trials, dosages are not yet clearly established. Some common doses administered in clinical trials include 250 mg of NMN or 1,000 mg of NR.
Consult with your medical provider before determining your intake amount. Supplement manufacturers may formulate products differently, so always read the labels and suggested serving size.
There is not enough research data to say that NAD supplements are safe. While niacin is naturally found in foods, it’s unknown how higher doses or longer-term supplementation can affect the body. The other niacin derivatives, like NAD, NMN, and NR, have unknown safety profiles. Your medical provider can help answer your questions about NAD supplements and how they may affect you.
People with liver or kidney issues, who are pregnant, or who are breastfeeding should not take NAD supplements since the impacts are unknown.
Like other supplements, NAD may interact with other medications and supplements. Be sure that your medical provider knows what you take so they can accurately advise you.
NAD supplements and other B vitamins can be taken with or without food, since they are water-soluble compounds. Since they can influence cellular energy, most recommendations suggest taking them earlier in the day is better.
Several foods contain precursors of NAD, including meat, poultry, seafood, dairy products, fortified grains, broccoli, avocado, cabbage, and soy.
NAD and NADH are different metabolites of the same nutrient, but they have different functions within cells. NAD+ is needed for DNA repair, gene expression, and numerous enzyme reactions. NADH is primarily involved with cellular energy and ATP generation. Both are important, but one does not replace the other. They can each be converted to the other one in the body as needed.
Yes, fatigue is one of the possible side effects of NAD. However, most side effects of NAD are mild and are not experienced by everyone. Other possible side effects include headaches, muscle discomfort, leg cramps, and nausea.
NAD is an important nutrient derivative that is needed for cellular energy, DNA health, and more. More studies are needed to really understand how NAD works and what benefits it consistently offers. Additionally, it’s important to develop a better safety profile for long-term use.
If you’re interested in NAD, talk to your healthcare provider about the potential benefits, risks, and alternatives.