What Is Nicotinamide Riboside? (Niagen®) - We Give You The Facts on Aging, Hearing, Energy and More
NR Benefits, Dosage, Studies and Synergistic Supplements
This recently discovered nootropic is associated with supporting cognitive function, healthy aging, and improvements in metabolism. Some of its potential health benefits in which it may be involved include:
- Boosts NAD+ levels
- Cellular age
- Protection against cell damage
- Support aging of skeletal muscle
- Resistance to weight gain
- Supporting cellular energy and communication
- Protecting against noise induced hearing impairment
- Improving Metabolism
- Supporting a healthy cardiovascular system
- Elevates Mood
- May improve skin and gives a more youthful appearance
What is Nicotinamide Riboside?
Nicotinamide Riboside is a form of vitamin B3 that acts as a vitamin precursor to NAD+[1]. It is also known to be an activator of Sirtuin. These enzymes are involved in the catalysis of NAD+ and are known energy (calorie) restriction mimetics.
Sirtuins therefore play a role in the healthy ageing effects associated with calorie restriction diets[2]. Nicotinamide Riboside (NR) is also known and distributed as Niagen® .
NR is attracting especial interest in the fields of nootropics and bodybuilding as it is associated with supporting brain performances, such as mental focus and memory support, protecting against neuronal degeneration of axons, healthy aging, improving skin quality, supporting cellular metabolic processes and thermogenesis, protecting against loss of hearing, and promoting healthy muscle performance and endurance as one ages.
NAD+ Biological Processes
Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that is found in all cells. It exists in two forms: NADH (reduced form) and NAD+ (oxidized form). NAD is known to:
- Have a major role in metabolism, where it is involved in the transfer of electrons between molecules.
- Carries electrons in the form of NADH from the cytoplasm into the mitochondrion
- Plays a large role in the production of energy through the creation of ATP
- Nicotinamide Riboside is converted into NAD+ by enzymes located in the nucleus (the cell’s information center.
- Involved in DNA repair and replication
- Removes acetyl groups from proteins that are caloric restriction mimetic candidates
It plays a major role in cellular metabolism. NAD acts as an electron carrier in redox biochemical reactions. The main metabolic role of NAD+ is to act as an acceptor of electrons, upon gaining an electron it becomes reduced to form NADH. It is then able to donate (transfer) electrons to other molecules.
This means that NAD+ plays a very important role in the release of energy from nutrients in the redox metabolism. Upon oxidation of glucose and fatty acids, energy is passed to NAD+ during processes such as glycolysis, beta-oxidation, and in the citric acid cycle (Krebs cycle; TCA cycle).
As well as acting as an electron carrier, NAD is a substrate of enzymes involved in post-translational modifications. It is a substrate of DNA ligases (enzymes involved in DNA repair and replication).
As well as being able to create NAD+ from amino acid precursors, cells can also create NAD+ via salvage pathways from three vitamin precursors: nicotinamide; nicotinic acid; and Nicotinamide Riboside.
Most of the enzymes that are involved in salvaging Nicotinamide Riboside and the other precursors are located in the nucleus; the information-processing center of the cell, where DNA is stored. NAD+ is also involved in cell-to-cell signaling.
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NAD+ and Sirtuin-Activating Compounds (STAC)
- These are compounds that mimic the healthy aging effects of low calorie diets
In addition to its roles in metabolism and DNA ligation, NAD+ is used by sirtuins.
These proteins are known to have an influence on numerous processes, such as the circadian clock; in the cell they play a role in aging, inflammation, apoptosis, and transcription.
Sirtuins have also been reported to play a major role under low calorific conditions, where they are able to improve energy efficiency and enhance mental alertness[3].
Another example of a STAC available as a supplement is RESVERATROL, which can prolong lifespan (in obese mice) through DNA repair and by regulatory changes in the expression of age related genes.
Nicotinamide Riboside VS Nicotinamide and Niacin
Clinical trials have recently shown that Nicotinamide Riboside taken orally is able to boost NAD+ metabolism in humans[4]. It was demonstrated that Nicotinamide Riboside produces a greater amount of NAD+ stimulation than the two other NAD+ precursor B3 vitamins, nicotinamide and niacin.
Healthy Aging
- Decreases in NAD+ levels are linked to age-related decay of cellular structures such as the mitochondria
- Increases mitochondrial mass
- Induces mitochondrial biogenesis and oxidative metabolism
- These help to support and control aging processes
As people age there is a natural decrease in their levels of NAD+. This leads to a loss of efficiency in ATP energy production in the mitochondria and in poorer communication with the nucleus[5].
Oral Supplementation with Niagen nicotinamide riboside has been shown to boost levels of the coenzyme NAD+[6].
- Increases in NAD+ levels resulting from nicotinamide riboside supplementation are dose dependent
- Nicotinamide riboside is the favored NAD+ precursor in the mitochondria
A clinical trial performed at University of Iowa health Care involving both mice and humans indicates that taking nicotinamide riboside supplement is safe for humans, is orally bioavailable, and boosts levels of the important cell metabolite NAD+. [4]
The trial involved 12 healthy humans (50% women; 50% men). They were provided oral dosages of 100 mg, 300 mg, or 1 g of nicotinamide riboside, with a seven-day dosage gap. It was found that increases in the level of NAD+ were dependent on the dose given, with greater amounts of nicotinamide riboside supplementation leading to greater increases in NAD+ levels. There were no serious health effects reported during the clinical trial.
One company also performed clinical trials [7]. They looked at the effects of giving a combination of 250 mg nicotinamide riboside and 50 mg Pterostilbene supplementation to 120 elderly people (seniors) aged 60-80 over an eight week long study. They reported a 40% increase in NAD+ levels in the blood after four weeks of supplementation. This level was maintained.
As 250mg is considered a normal dosage of nicotinamide riboside, they then took a look at the impact of increasing the dosage levels to 500 mg. They reported that NAD+ was increased by ~90% after four weeks at this increased supplementation level, and that these increased levels were maintained throughout the course of the study. Like in the previous study [4], no adverse safety effects were recorded during the study-period.
Hearing Loss and Neuroprotection
Work carried out at the Weill Medical college of Cornell university has revealed that supplementation with nicotinamide riboside is able to provide support for improving hearing in mice that have suffered noise-induced hearing damage[8]. Supplementation increases NAD+ levels, which in turn acts to protect damage to neuron axons. These NAD+ protective effects are driven by the activation of mitochondrial sirtuins.
Reversal of Age Related Skeletal Muscle Loss by Restoration of NAD+
More and more derogatory age related phenotypes are being reported to be reversible.
Age associated defects of skeletal muscle occur because of oxidative phosphorylation defects [9]. When animals reach old age the expression levels of mitochondrial and nucleus genes involved in oxidative phosphorylation are massively reduced. This leads to a diminished reliability of mitochondrial DNA.
The restoration of NAD+ levels through supplementation with precursors such as nicotinamide riboside is expected to intervene in mitochondria aging. In addition to support skeletal muscle loss, supplementation is also expected to have whole body benefits such as supporting circadian clock function and hematopoietic stem cell (hemocytoblasts) production.
Increased Energy Benefits
Some of the secondary benefits associated with restoration of NAD+ levels include increased calorie burning caused by enhanced metabolism; and an increased production of ATP; a molecule that plays an important role in maximizing muscle performance and in maintaining energy levels.
Further Published Reading Evidence
Wikipedia:
- Sirtuin-activating compounds [https://en.wikipedia.org/wiki/Sirtuin-activating_compound]; Energy restriction mimetics
- [https://en.wikipedia.org/wiki/Caloric_restriction_mimetic]; Nicotinamide adenine dinucleotide + nadp
- [https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide#Oxidoreductase_binding_of_NAD]
Examine:
- [https://examine.com/]
WebMD:
- Use of Vitamin B3 to treat those with High Cholesterol [http://www.webmd.com/cholesterol-management/nicotinic-acid-for-high-cholesterol]
Reddit:
- Subreddit on NR, includes test information from mouse and rats diabetes researchers[https://www.reddit.com/r/NicotinamideRiboside/]
References/Citations
[1] Yang and Sauve. NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta. 2016 Dec;1864(12):1787-1800. doi: 10.1016/j.bbapap.2016.06.014
[2] Corbi et al. Role of sirtuins, calorie restriction and physical activity in aging. Front Biosci (Elite Ed). 2012 Jan 1;4:768-78.
[3] Imai and Guarente. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002.
[4] Samuel et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications, 2016; 7: 12948 DOI: 10.1038/NCOMMS12948
[5] Nikiforov et al. Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation. J. Biol. Chem. 286, 21767–21778.
[6] Chi and Sauve. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):657-61. doi: 10.1097/MCO.0b013e32836510c0.
[7] ELYSIUM HEALTH Press Release: [https://www.elysiumhealth.com/clinical-trial-press-release]
[8] Brown et al. Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 2014 Dec 2;20(6):1059-68. doi: 10.1016/j.cmet.2014.11.003.
[9] Mendelsohn and Larrick. Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levels. Rejuvenation Res. 2014 Feb;17(1):62-9. doi: 10.1089/rej.2014.1546.
Frequently Asked Questions
Which foods contain Nicotinamide Riboside?
Trace amounts of Nicotinamide Riboside are naturally found in dairy products such as milk, yoghurt, and cheese, and in foods containing yeast.
What were the findings of the initial study into the effects of NR? How was Nicotinamide Riboside discovered?
The initial discovery of Nicotinamide Riboside was by Charles Brenner, who now acts as a consultant for ChromaDex (the manufactures of NIAGEN®). He found that taking 1 g of NR a day for seven days increased the levels of NAD+ in his blood 2.7-fold, and there was also a 45-fold increase in the levels of NAAD.
Will this supplement help with fat loss?
As NR helps to both maintain and increase metabolism in the energy producing centers of the cell it is is likely to be an associated with support of calorie burning. However, NR should not be thought of as a weight-loss supplement.
Ideally losing weight will require a combination of a healthy diet and an exercise regime. It is always a good idea to lose the odd kilogram if you are obese.
What benefits of NAD+ have been reported in scientific studies? What is it good for?
In mice, scientists showed that increased levels of NAD+ are associated with supporting various aspects of cardiovascular health, energy, muscle soreness, hearing, vision, and sleeping, and muscle ageing.
Nicotinamide riboside (NR)
- vs NADH: It is a precursor to NAD+ and NADH
- vs niacinamide: See below
- vs Nicotinamide: NR is more effective in practice
- vs and Niacin: NR is more effective
- vs Niagen®: Niagen is the trademark for NR
- Vitamin B3: NR is a form of this vitamin, but they act different in practice
What is the difference between Niacin and Niagen?
They are both forms of vitamin B3 and act as precursors to NAD+. Niagen, the trademark for the pyridine nucleoside Nicotinamide riboside has greater bioavailability and uptake in the mitochondria.
Will it affect my dreams?
Some people have reported that they have better recall of their dreams when taking NR. This is possibly due to increased neuron activity. Research is required in this area to support their claims.
Will it improve my skin and prevent flushing?
Many people have reported that their skin feels smoother and that they feel it might make them have a much younger appearance. Again, scientific research is required into this topic.
What other supplements are recommended for healthy aging and support of brain health?
One of the major human trials performed on Nicotinamide Riboside was while used in conjunction with a Pterostilbene Supplement (Available from VitaMonk)
Niagen is also frequently taken along side of resveratrol. Resveratrol is similar in nature to pterostilbene, and is frequently referred to as "the healthy stuff in red wine" in popular culture. To capture the best of both products (they most likely work synergistically) we provide a pterostilbene with resveratrol supplement.
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