An Overview of Niacin, Niacinamide, NR, and NMN

What Is Vitamin B3?

Vitamin B3, also known as niacin, is a critical water-soluble vitamin that supports numerous metabolic and cellular functions. In addition to niacin, derivatives such as niacinamide, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN) have gained significant attention due to their role in maintaining cellular energy and promoting healthy aging. These compounds primarily function by contributing to the synthesis of NAD+ (nicotinamide adenine dinucleotide), a coenzyme essential for energy metabolism and cellular repair processes[i].

Vitamin B3 exists in several forms, each with distinct physiological roles:

Niacin (Nicotinic Acid)

Niacin is often recognized for its lipid-modifying properties, including the ability to reduce LDL cholesterol and increase HDL cholesterol, making it a valuable tool in cardiovascular health. One noted side effect is flushing, a temporary reddening of the skin due to vasodilation[ii].

Niacinamide (Nicotinamide)

Unlike niacin, niacinamide does not cause flushing. It is frequently used in dermatology for its anti-inflammatory effects and ability to improve the skin barrier, benefiting conditions such as acne and eczema[iii].

Nicotinamide Riboside (NR)

NR is a direct precursor of NAD+ and has been shown to enhance mitochondrial function, support neuroprotection, and combat age-related metabolic decline. Its ability to increase NAD+ levels has made it a focus of anti-aging research.[iv]

Nicotinamide Mononucleotide (NMN)

NMN is another NAD+ precursor that has gained traction for its potential to mitigate age-related decline in NAD+ levels. Preclinical studies suggest that NMN supplementation may improve mitochondrial function and physical performance[v].

The Functions of Vitamin B3

Vitamin B3 and its derivatives play a central role in cellular metabolism and repair by contributing to NAD+ production. Specifically, NAD+ is essential for:

Energy Metabolism: NAD+ is pivotal in converting nutrients into cellular energy through the mitochondrial electron transport chain[vi].
DNA Repair: NAD+ supports enzymes such as PARPs (poly-ADP-ribose polymerases), which repair damaged DNA[vii].
Cellular Signaling: NAD+ regulates stress responses and longevity pathways, including sirtuins, which influence aging and metabolic health[viii].
Oxidative Stress Management: Through its role in cellular redox reactions, NAD+ helps neutralize free radicals and reduces oxidative damage[ix].

Why Do NAD+ Levels Decline Over Time?

NAD+ levels naturally diminish with age, leading to reduced mitochondrial efficiency and impaired cellular function. The primary reasons for this decline include:

Increased NAD+ Consumption: Enzymes like PARPs and CD38, which become more active as DNA damage accumulates, deplete NAD+ reserves[x]
Reduced Synthesis: With aging, the body’s ability to generate NAD+ from precursors declines[xi].
Lifestyle Factors: Poor nutrition, chronic stress, and environmental toxins exacerbate NAD+ depletion[xii].

The reduction in NAD+ levels is associated with age-related conditions such as metabolic disorders, neurodegeneration, and weakened immunity[xiii]. The following graph shows the significant decline in NAD+ over time:

Approximate values based on studies using 20-year-olds at 100%. Notice that by age 60, NAD+ levels may be ~50% of youthful levels. (e.g., Massudi et al., 2012; Zhou et al., 2016).

How to Prevent NAD+ Decline and Sustain Energy

Regular Physical Activity

Exercise stimulates mitochondrial biogenesis and improves NAD+ production pathways. High-intensity interval training and endurance exercises have shown particular efficacy[xiv].

A Nutrient-Dense Diet

Because all the precursors for NAD+ are found in food, foods rich in tryptophan and Vitamin B3, such as poultry, fish, whole grains, and nuts, support NAD+ biosynthesis.

Here’s a concise list of foods high in vitamin B3 (niacin) with their approximate content per 100 grams, based on reliable nutritional data:

Beef Liver (cooked): 16.7 mg
Chicken Breast (cooked): 14.8 mg
Peanuts (roasted): 13.5 mg
Tuna (canned in water): 10.5 mg
Salmon (cooked): 10.1 mg
Mushrooms (white): 4.5 mg
Peas: 2.0 mg
Avocado: 1.7 mg
Eggs 0.9 mg
Brown Rice (cooked): 0.7 mg

Green vegetables, grains, potatoes, and other vegetables are not a great source vitamin B3. The other source is tryptophan, an amino acid found in meat, poultry and fish.

You can see that you will not get a large amount of vitamin B3 from the diet. Even those meats high in nicotinamide, such as chicken breast, a 4-ounce serving provides about 15 mg. This is very low compared to the dose of a supplement, which is usually 100 – 500mg.

Another dietary way to increase NAD+ is a ketogenic diet. It may be essential to prevent aging because the constant carbohydrates lower the ability of the mitochondria to burn fat for energy. We need about 60% of our energy to come from fat, but insulin blocks this. A ketogenic diet has been shown to increase NAD+ in the brain, preventing seizures, and neurodegenerative diseases[xv]

Caloric Restriction and Fasting

Intermittent fasting and caloric restriction activate sirtuins and other pathways dependent on NAD+, enhancing mitochondrial efficiency[xvi]. Intermittent fasting – 16 hours per day from 5:00 PM to 9:00 AM works well. The optimum long-term fast to maintain mitochondrial energy and prevent the effects of aging is 72-hours once a month. Start in the morning on Friday, for example, and eat again on Monday morning. Drink water when thirsty.

Stress Management

Minimizing stress and reducing exposure to environmental toxins help preserve NAD+ levels. Practices such as mindfulness meditation and ensuring adequate sleep are beneficial[xvii]. Sleep 7-8 hours every night at the same time. Sleep by 10:00 PM and wake up by 6:00 AM to maintain good adrenal function.

Detoxification

Alcohol and sugar deplete NAD+ in the cells.[xviii] Many of the drugs people take on a daily basis inhibit NAD precursors or the production of NAD+.[xix] For example, statins decrease CoQ10 which lowers NAD+. Your medications, along with alcohol and sugar, might be lowering your energy levels.

Supplementation with NAD+ Precursors

Research demonstrates that supplementation with NR or NMN can effectively restore NAD+ levels, enhancing mitochondrial function and physical endurance[xx]. Nicotinamide Riboside (NR) is the most studied form. The optimal dose is about 1000mg once per week.

IV NAD+ Therapy vs. Oral Supplements

What Is IV NAD+ Therapy?

Intravenous (IV) NAD+ therapy entails directly infusing NAD+ into the bloodstream, bypassing the digestive system. This method allows for higher plasma concentrations. Interestingly, the NAD+ is not taken into cells as such, but is converted to other precursors, such as Nicotinamide Riboside (NR) and others that are taken up into cells and then made into NAD+.

Benefits of IV NAD+ Therapy

Immediate Absorption: IV therapy ensures near-instant availability for cellular use, bypassing potential losses during digestion.
Higher Plasma Levels: This method can achieve greater NAD+ blood levels compared to oral supplementation[xxi].
Potential Therapeutic Benefits: Anecdotal evidence suggests IV NAD+ therapy may alleviate symptoms of chronic fatigue and support recovery in neurological conditions[xxii].

Limitations of IV NAD+ Therapy

Cost: IV therapy is significantly more expensive than oral supplements.
Inconvenience: Sessions can take several hours and may require specialized facilities.
Side effects such as nausea and flushing and flushing may occur.
Infrequent dosing may not maintain high levels of NAD+

Oral Supplements: A More Practical Approach

While less immediate, oral precursors like NR and NMN provide a steady and sustainable way to maintain NAD+ levels. They are more accessible, cost-effective, and convenient for long-term use.

The choice between IV NAD+ therapy and oral supplements depends on individual health needs and financial considerations. For those seeking rapid results, IV therapy may be more suitable, whereas oral supplementation is ideal for ongoing maintenance and preventative care.

Since Nicotinamide Riboside (NR) is 50-70% bioavailable, meaning it is absorbed and used in the body, there is no need for most people to use IV therapy. You can essentially do the same thing with a weekly oral double dose to raise the levels of NAD+ in your cells[xxiii].

Another advantage of using a NR supplement is that the body won’t need to shunt the tryptophan to making more NAD+, taking away from serotonin and melatonin. As people age, not only does the NAD+ decrease, but serotonin also decreases, causing more depression[xxiv]. Taking a vitamin B3 supplement helps to allow your dietary tryptophan to be made into melatonin instead of NAD.

Conclusion

Vitamin B3 and its derivatives, including niacin, niacinamide, NR, and NMN, are integral to sustaining cellular energy and longevity. By understanding their roles in NAD+ metabolism and implementing strategies to counteract its decline, individuals can enhance mitochondrial function and overall vitality. Through supplementation, lifestyle changes, or advanced therapies like IV NAD+, maintaining NAD+ levels offers a promising pathway to healthier aging[xxv]

7 Ways to Increase Your NAD+ And Prevent Aging:

Exercise Regularly – use HIIT exercises to keep your mitochondria functioning well.
Keep an 8-hour window of eating. Stop by 6pm.
Monthly Fast – 72 hours once per month.
Avoid toxins: Sugar, alcohol, MSG, drugs.
Lower stress – get good sleep, meditate daily, take walks, forgive everyone, enjoy the ride, be happy.
Supplement – take NR about 1,000mg per week, either all at once, or divided into multiple doses.
Eat a ketogenic diet with less than 20g of carbs per day for 30 days once a year to keep mitochondrial fat-burning capacity.

NAD+ and Vitamin B3: Unlocking Cellular Energy and Promoting Longevity

What Is Vitamin B3?

Niacin (Nicotinic Acid)

Niacinamide (Nicotinamide)

Nicotinamide Riboside (NR)

Nicotinamide Mononucleotide (NMN)

The Functions of Vitamin B3

Why Do NAD+ Levels Decline Over Time?

How to Prevent NAD+ Decline and Sustain Energy

Regular Physical Activity

A Nutrient-Dense Diet

Caloric Restriction and Fasting

Stress Management

Detoxification

Supplementation with NAD+ Precursors

IV NAD+ Therapy vs. Oral Supplements

What Is IV NAD+ Therapy?

Benefits of IV NAD+ Therapy

Limitations of IV NAD+ Therapy

Oral Supplements: A More Practical Approach

Conclusion

7 Ways to Increase Your NAD+ And Prevent Aging:

[viii] Review Genes Dev. 2006 Nov 1;20(21):2913-21. doi: 10.1101/gad.1467506.

Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction

Marcia C Haigis, Leonard P Guarente

[ix] Review Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002.

NAD+ and sirtuins in aging and disease; Shin-ichiro Imai, Leonard Guarente

[xi] Mechanisms of Ageing and Development; Volume 206, September 2022, 111707

Oxidative stress, aging, antioxidant supplementation and their impact on human health: An overview

Giovanni Martemucci, Piero Portincasa, Agostino Di Ciaula, Michele Mariano, Vincenzo Centonze, Angela Gabriella D’Alessandro

[xii] Science. 2015 Dec 4;350(6265):1208-13. doi: 10.1126/science.aac4854.

NAD⁺ in aging, metabolism, and neurodegeneration

Eric Verdin

[xiii] Ibid.

[xv] Front Mol Neurosci. 2017 Nov 14;10:377.

Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?

Marwa Elamin

[xvii] Cell Metab. 2010 Mar 3;11(3):213–219. doi: 10.1016/j.cmet.2010.02.006

Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle

Carles Cantó, et al.

[xxiii] Nat Communications. 2016 Oct 10:7:12948. doi: 10.1038/ncomms12948.

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

Samuel A J Trammell, et. al.

[xxiv] Cell Metab. 2014 Feb 4;19(2):178-80. doi: 10.1016/j.cmet.2014.01.005.

NAD+ deficiency in age-related mitochondrial dysfunction

Tomas A Prolla, John M Denu

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