NAD (Nicotinamide Adenine Dinucleotide) is a natural compound found in the body. It is an essential cofactor for enzymes, such as sirtuins and PARPs, that are responsible for regulating the body’s response to inflammation and damage. It has gained much popularity in the anti-aging community, and this article will cover the biggest reasons why.

What is NAD+

NAD+ is the oxidised form of NAD, while NADH is the reduced form. NAD is cycled between its oxidised and reduced forms through redox reactions catalysed by various enzymes.

It can be synthesised from several precursors, including nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Each of these molecules enters different biosynthetic pathways to generate NAD+.

NAD+ and Aging

With people being able to live longer, age-related illnesses are more prevalent now than ever before. Although prolonging the human life span may appear to be a great accomplishment, it is of little value if this extra time is not lived in good health.

There are many measurable markers that we know we can expect to either rise or decline with age. When we know it is to be expected that our inflammatory markers will increase and levels of our sex hormones will decrease as we get older, it is easy to submit to these changes and their negative consequences, unquestioningly. But if we do not so readily accept the inevitable and instead attempt to delay it, perhaps we can maintain the quality of our health for longer.

NAD+ is one of these markers that declines with age, while NADH increases. This imbalance between the oxidised and reduced states of NAD, in particular the decline in NAD+, is strongly linked to an increase in age-related diseases¹, making it a subject of great interest amongst anti-aging researchers.

Why Does NAD+ Decline with Age?

The decline in NAD+ can be attributed to several factors, including a decrease in the production of NAD+ itself, an increase in its degradation by enzymes such as CD38, and changes in tissue composition¹.

CD38 plays a major role in the decrease in NAD+ that is seen with aging. It becomes more active with advancing age and is upregulated by pro-inflammatory signals from senescent cells and macrophages. With CD38 metabolising NAD+ at an increased rate, cells are unable to synthesise enough NAD+ to keep up with the body’s needs. Sirtuins and PARPs also tend to consume more NAD+ in response to the increased DNA damage and stress that happens as we age. To make matters even worse, NAD+ biosynthesis tends to decrease. This leads to a disruption in DNA repair, mitochondrial function and metabolic regulation, all of which increase the risk of disease².

Diseases Linked to NAD+ Deficiency

NAD+ deficiency is associated with several age-related diseases¹, such as:

Alzheimer’s disease
Parkinson’s disease
Glaucoma
Macular degeneration
Diabetes
Cardiovascular disease
Cancer
Sarcopenia and frailty
Mitochondrial dysfunction

This link between NAD and aging is a topic that gained traction in the early 2000s. Since then, researchers have investigated methods of increasing NAD+ levels through various means in an attempt to slow the effects of aging and reduce the likelihood of developing age-related diseases.

Increasing NAD+ Through Supplementation

One of the most popularly explored methods is by supplementing with precursors of NAD. Administration of NAD+, either orally or intravenously, has been tested by some research groups.

Benefits Seen in Animals

So far, results have looked promising, with animal models demonstrating:

Improved glucose and lipid metabolism³
Weight reduction⁴
Reduced diabetes risk⁵
Protection from heart and kidney disease⁶
Reversed vascular dysfunction⁷
Slowed neurodegeneration⁸
Rejuvenation of stem cells and increased life span⁹

Essentially, increasing NAD+ levels helps to improve healthspan and promote longevity.

Benefits Seen in Humans

In humans, studies have been relatively short, so the effects that have been observed so far have been more subtle when compared to animal tests.

Improved Sensitivity to Insulin and Muscle Remodelling

A study involving prediabetic women found that increasing NAD+ through NMN supplementation increased the sensitivity of muscle tissue to insulin, improved insulin signalling and increased muscle remodelling and regeneration¹⁰.

Improved Exercise Performance

Since a link between precursor supplementation and an improvement in the exercise performance of mice has been observed, a research group attempted to test whether this benefit could be replicated in humans. The researchers found that the aerobic capacity of amateur runners was increased after 6 weeks of daily NMN supplementation¹¹.

Improved Cardiovascular Health

In another study, NAD+ metabolism was stimulated by supplementing healthy, middle-aged and older subjects with NR. This caused a reduction in systolic blood pressure and a decrease in arterial stiffness, demonstrating a promising improvement in cardiovascular health¹².

Other Benefits

A mini review on NAD+ and its potential to improve cardiometabolic health mentions several studies that suggest increasing NAD+ may help improve glucose levels, alter body composition, decrease blood pressure and reduce inflammation. It also highlighted an important observation, which was that there were significant differences in the improvements seen depending on the gender of the participants. Increasing NAD+ levels were found to offer no benefit in some studies, this is thought to be because the subjects were already healthy or had no NAD+ deficiency¹³.

Doses Used

By looking at the studies that have been done on humans, we can see that people are typically given doses of anything from 100 to 2000mg of precursor. When NAD+ is given intravenously, it is most commonly given as a dose of 500mg.

Safety

Precursors are generally well tolerated when taken at standard doses. Although some precursors have shown protective effects on the brain after ischemic events, evidence suggests they may sensitise the brain to damage from such events if taken beforehand¹⁴. If taken in chronically high doses, NAM may inhibit enzymes responsible for protecting genome integrity and alter gene expression¹⁵.

When an NAD+ infusion (500mg) was given to healthy adults, temporary discomfort during the process of infusion was documented. Nausea, headaches, diarrhoea and muscle tightness were experienced, resulting in the need for longer infusion times to reduce side effects¹⁶. There have been no recorded cases of people overdosing on NAD+.

Other Ways to Increase NAD+

In addition to supplementation, there are other ways to help increase NAD+ levels as well, such as:

Regular exercise
Caloric restriction
Fasting
Consuming foods rich in NAD+ precursors
Consuming polyphenol-rich foods

Conclusion

NAD+ levels naturally drop as we age, which can lead to an increased risk of health problems. Given that NAD+ is an essential cofactor in enzymatic reactions that regulate vital cellular processes, it comes as no surprise that a lack of this compound leads to problems. However, this decline in NAD+ can be mitigated in some cases, potentially improving health, through supplementation and lifestyle changes.

If you’d like to explore NAD+ for yourself, quality supplements are available here.

References

Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22(2):119-141. doi:10.1038/s41580-020-00313-x
Strømland Ø, Diab J, Ferrario E, Sverkeli LJ, Ziegler M. The balance between NAD+ biosynthesis and consumption in ageing. Mech Ageing Dev. 2021;199:111569. doi:10.1016/j.mad.2021.111569
Escande C, Nin V, Price NL, et al. Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38. Diabetes. 2013;62(4):1084-1093. doi:10.2337/db12-1139
Roh E, Myoung Kang G, Young Gil S, et al. Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice. Obesity. 2018;26(9):1448-1456. doi:10.1002/oby.22263
Yoshino J, Mills KF, Yoon MJ, Imai S ichiro. Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metab. 2011;14(4):528-536. doi:10.1016/j.cmet.2011.08.014
Morevati M, Egstrand S, Nordholm A, et al. Effect of NAD+ boosting on kidney ischemia-reperfusion injury. Câmara NOS, ed. PLOS ONE. 2021;16(6):e0252554. doi:10.1371/journal.pone.0252554
de Picciotto NE, Gano LB, Johnson LC, et al. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell. 2016;15(3):522-530. doi:10.1111/acel.12461
Zhao Y, Zhang J, Zheng Y, et al. NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway. J Neuroinflammation. 2021;18(1):207. doi:10.1186/s12974-021-02250-8
Zhang H, Ryu D, Wu Y, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-1443. doi:10.1126/science.aaf2693
Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. doi:10.1126/science.abe9985
Liao B, Zhao Y, Wang D, Zhang X, Hao X, Hu M. Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study. J Int Soc Sports Nutr. 2021;18(1):54. doi:10.1186/s12970-021-00442-4
Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. doi:10.1038/s41467-018-03421-7
Blanco-Vaca F, Rotllan N, Canyelles M, Mauricio D, Escolà-Gil JC, Julve J. NAD+-Increasing Strategies to Improve Cardiometabolic Health? Front Endocrinol. 2022;12:815565. doi:10.3389/fendo.2021.815565
Qu W, Ralto KM, Qin T, et al. NAD+ precursor nutritional supplements sensitize the brain to future ischemic events. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2023;43(2_suppl):37-48. doi:10.1177/0271678X231156500
Hwang E, Song S. Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment. Biomolecules. 2020;10(5):687. doi:10.3390/biom10050687
Hawkins J, Idoine R, Kwon J, et al. Randomized, placebo-controlled, pilot clinical study evaluating acute Niagen®+ IV and NAD+ IV in healthy adults. medRxiv. Preprint posted online June 10, 2024:2024.06.06.24308565. doi:10.1101/2024.06.06.24308565

Which SARM is the best for muscle gain?

It can be difficult to determine which SARMs are best for lean muscle building because different body types respond differently to them. Almost all SARMs boost muscle gain, but some have a stronger effect than others.

Top-tier SARMs for muscle gain include:

Test RAD-140
Ibutamoren MK-677
Ostarine MK-2866

Compared to some other brands, they also offer really good performance. RAD-140, Ostarine, and MK-677 are well-known for boosting muscle growth explosively and making gaining muscle much easier.

If you want to gain a lot of muscle quickly, consider using one of the above SARMs.

Do SARMs have side effects?

SARMs’ side effects are generally fewer and less serious than those of anabolic steroids. Still, using SARMs supplement products does have a small risk of complications.

Some side effects that have been reported include:

Diarrhoea
Headaches
Hypertension
Heart disease
Aggression
Acne

It is important to remember that the severity and presence of a side effect will likely depend on both dosage and the specific SARM taken.

Why should I use SARMs?

Burning fat
Bulking or cutting
Improving performance
Decreased recovery time
Building lean body mass
Increasing bone density

What are SARMs?

SARMs, or selective androgen receptor modulators, are relatively new drugs that attach to your body’s androgen receptors, triggering changes in your DNA, which in turn increases your muscles’ ability to grow. Unlike steroids, they target specific types of tissues and don’t come with side effects like breast growth in males.

They combat muscle loss caused by age, osteoporosis, disease, and building muscle and bone. Due to their ability to improve strength with fewer side effects than steroids, dietary supplement brands have started selling them to athletes.

Because they’re anabolic agents that enhance performance, SARMs are on the World Anti-Doping Agency’s list of prohibited substances.

How long should I wait between SARM cycles?

SARM cycles are intense, and you need to recover between them to ensure you don’t end up with long-term damage.

On average, SARM cycles last 8-12 weeks, and Post Cycle Therapy lasts 2-4 weeks. So if you want to start another SARM cycle, it’s important to wait until after your PCT. When your hormone and testosterone levels are back where they should be, you can begin another SARMs cycle.

After your PCT, you can continue to aid your training with another muscle building supplement stack to help restore muscle and maintain results from your previous SARMs cycle. Whether you’re using a cutting stack, a weight gainer bundle, or looking for the best stack for muscle growth, prioritising recovery helps you stay on track. Take the next step only when you’re ready.