What are NAD+ precursors and how much should you take?

The world’s population is aging. As the number of people aged 60 and over increases, scientists are hard at work exploring compounds that can help us tread the path to longevity, and focus on healthy aging, rather than inevitable decline.

The result is supplements, and certain supplements can help you tackle aging at a cellular level. Boosting cell energy production with NAD+ precursors can slow age-related organ and tissue function deterioration and help keep you healthier for longer.

What is NAD+?

NAD⁺ is short for nicotinamide adenine dinucleotide [1]. It is a vital coenzyme needed by every living cell in your body to sustain cellular energy production and repair and defence processes. 

Without NAD+, we would be on the fast track to deterioration. This molecule plays a key role in many cellular operations, cell generation and mitochondrial function. NAD+ assists the conversion of food to energy, plays a vital role in preserving DNA integrity and ensures proper cell function to defend our bodies from aging and disease.

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What are NAD+ precursors and how do they work?

To produce NAD+, cells use building blocks called NAD+ precursors. A precursor is a smaller building block that is used to help form a larger molecule. 

These precursors undergo a set of chemical transformations that result in the production of NAD+. Dietary NAD⁺ precursors like nicotinamide riboside, niacin and nicotinamide are the building blocks that cells use to produce more NAD+. 

Although the structures and names names of these NAD+ precursors are barely similar to the drug nicotine in tobacco, these molecules are incredibly distinct and produce different results in the body [2]. Additionally, their disparities make one toxic and the others essential.

Established NAD+ precursors 

Nicotinic acid (NA):  commonly known as niacin, it is a form of vitamin B3 found in the late 30s. Niacin was seen to cure a disease called pellagra, the late stage of severe niacin deficiency. 

Pellagra was common in the southern US in the early 1900s when income was low, and corn products were a major dietary staple. The disease is characterised by diarrhea, dementia, dermatitis, and eventually death [3]. 

Niacin is present in beans, cereal grains, eggs, fish, green vegetables, meat, milk and yeast [4]. There is a recommended daily allowance or RDA of NA, at the rate of 14 niacin equivalents (NE) for women. On the other hand, 16 NE (1 mg NE = 60 mg of tryptophan = 1 mg niacin) is the requirement for men. Niacin utilises a three-step pathway, known as the Preiss-Handler pathway, through the cell to convert into NAD+ [5].

Nicotinamide (NAM): also known as niacinamide, is a form of vitamin B3 discovered in the late 1930s – around the same time as niacin. Nevertheless, nicotinamide became the more favourable vitamin B3, commonly used in nutritional supplements and food fortification, as it does not cause skin flushing [6].

Although nicotinamide is better accepted than niacin, in higher doses, it is known to inhibit important longevity promoting proteins within cells called sirtuins. Sirtuins are vital NAD-dependent enzymes critical in cellular metabolism and repair processes, helping to maintain and regulate cellular homeostasis [7]. Nicotinamide can be transformed into NAD+ through a two-step process via the salvage pathway.

Nicotinamide riboside (NR) is the third form of vitamin B3 discovered in the 1940s. Regardless, it was not until 2004 that its ability to increase levels of NAD⁺ was discovered [8]. 

Together, the same group of researchers that discovered NR’s NAD+ boosting ability also identified that NR is found in trace amounts in milk. Despite the fact that it is under the vitamin B3 category, NR has unique properties that differentiate it from both niacin and nicotinamide.

Unlike niacin, NR does not cause flushing, even at high doses and has been shown to be safe in human studies, even at doses as high as 2000mg a day and does not restrain sirtuins like nicotinamide. Actually, NR has been shown to activate sirtuins in multiple preclinical studies [9].

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Tryptophan (TRYP): a naturally occurring essential amino acid. It is consumed in the food rich in protein like eggs, seeds and meat. 

Once eaten, tryptophan can be utilised to make new proteins, the hormone melatonin and a molecule that works in the brain, serotonin. Also, it can be changed to NAD+ through an intricate, seven-step de novo pathway.

Considering its many uses, it is safe to believe that all tryptophan consumed does not go towards creating NAD+ [10]. Calculations to determine “niacin equivalents” revealed that 60 mg of tryptophan may have the same NAD+ raising ability as 1 mg of a B3 vitamin (niacin). Although, these may vary depending on the nutritional state of the consumer [11]. 

Tryptophan can be converted to niacin within the body as well. Although the effectivity of conversion is low and requires multiple steps.

Nicotinamide mononucleotide (NMN): last but not the least, NMN is not a form of vitamin B3. Regardless, it is an intermediate molecule made in the conversion of both nicotinamide and NR to NAD+ [12]. It is a kind of molecule termed as a nucleotide, something comparable to the building blocks of DNA. 

As a nucleotide, any NMN taken through food or supplementation must be converted to NR prior to entering the cell. Once in the cell, the NR is transformed back to NMN and subsequently to NAD+ [13].

How much NAD+ should I take?

The right NAD+ dosage will rely on the individual’s present health requirements and condition and the kind of precursor the supplement is using. It will be best to consult your doctor initially to generate a treatment plan. 

Most supplements will carry a recommended dosage of 250 to 300 mg daily, usually equal to one or two tablets. Even so, dosages have been used of between 100 mg and 1,200 mg a day [14]. There have been some notable side effects for larger dosages that reach 6,000 mg.

Some supplements will comprise of just the precursor itself, like nicotinamide riboside. Though some manufacturers may also combine it with other ingredients such as antioxidants, which may also have other effects.

The ideal dose level, will depend significantly on the kind of supplement being taken and the outcome you’re looking for. In the end, this will be a personal choice. 

Supplements may have diverse effects on different people. Commonly speaking, adhering to the recommended dose on the bottle will be safe and sufficient.

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The information included in this article is for informational purposes only. The purpose of this webpage is to promote broad consumer understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.

[1] https://www.nmn.com/precursors/what-is-nad
[2] https://lpi.oregonstate.edu/mic/vitamins/niacin
[3] https://pubmed.ncbi.nlm.nih.gov/14693013/
[4] https://www.efsa.europa.eu/en/efsajournal/pub/3759
[5] https://pubmed.ncbi.nlm.nih.gov/28899755/
[6] https://pubmed.ncbi.nlm.nih.gov/22646128/
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992043/
[8] https://bit.ly/3TRQNK7
[9] https://www.nature.com/articles/ncomms12948
[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487780/
[11] https://pubmed.ncbi.nlm.nih.gov/18429699/
[12] https://bit.ly/3ex6bvx
[13] https://www.ahajournals.org/doi/10.1161/circulationaha.116.026099
[14] https://www.nmn.com/news/how-much-and-for-how-long-can-i-take-an-nad-precursor

Photograph: MarySan/ShutterStock
The information included in this article is for informational purposes only. The purpose of this webpage is to promote broad consumer understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.