Staying young is something that we all desire, and recent scientific studies suggest that taking NAD+ precursors may significantly help with retaining a youthful appearance and healthy body function. However, when you begin researching the benefits of taking NAD+ precursors, you will be confronted by an alphabetical maze of different types of precursors; NA, NAM, NR and NMN.
NAD+ precursors are the building blocks that your cells require in order to create NAD+. A precursor is a tiny molecule that is utilised to make a larger one. These NAD+ precursors go through a series of chemical transformations to produce NAD+.
What is NAD+?
NAD+ is a coenzyme (a type of molecule), which is found in all living cells and plays a critical role in energy production and cellular repair and defence functions. It’s especially important for the health of our mitochondria, often called the ‘powerplant of the cell’, that convert food and oxygen into energy.
As we age, our levels of NAD+ begin to decline at an ever-increasing rate, impairing mitochondrial function, among other things. These substantially reduced NAD+ levels and subsequently poor cell function accelerates the aging process. It is believed that mitochondrial dysfunction and damage are major contributors to many age-related disease processes. Scientific evidence supports this theory as it has been shown that the rate and severity of age-related diseases increase as our NAD+ levels decline.
Benefits Of NAD+
Many cell enzymes in the human body require NAD+ to effectively modulate cell activity in response to both internal and external negative forces. It is critical that the health of these systems is maintained at all times and they can function correctly because the assaults on our cells are relentless. Our cells need to constantly combat the effects of environmental toxins, pro-inflammatory foods, and different sorts of trauma. Even things like certain medications can have negative impacts on our cells that must be balanced, mitigated, and/or repaired.
Given the importance of NAD+ to healthy cell function and the decrease of natural NAD+ levels as we age, we can see it is critical to do what we can to facilitate the creation of new NAD+ in our bodies. Currently, the best-known way to achieve this is by supplying the body with NAD+ precursors. Appropriate levels of Supplemental NAD+ precursors can support the body’s response to stress by ensuring healthy levels of NAD+ are maintained.
NAD+ is necessary for long-term health, well-being, and strength. Supporting appropriate levels of NAD+ has been scientifically proven to result in better memory, improved weight management and other benefits. NAD+ can achieve all of this because it activates sirtuin proteins, improves cell metabolic function and provides numerous other benefits.
Niacin and NAD+
Niacin (NA) has been known to the biomedical community for over 80 years. It was discovered by American biochemist Conrad Elvehjem, it is a water-soluble form of vitamin B3. NA has been used at high doses to treat high cholesterol for over 50 years, so its long-term effects are well documented and it is safe for long-term use. However, it has only recently been recognised as having significant benefits for treating NAD+ depletion and related metabolic disorders.
At the time of its discovery, niacin was called nicotinic acid because it can be produced by the oxidation reaction of nicotine and nitric acid. However, because of nicotine’s negative connotations due to its addictive properties and presence in tobacco products, scientists recognised the need to give it a name that lacked the obvious association with nicotine. The modern common name is derived from the full form of the chemical compound ‘NIcotinic ACid vitamIN’, aka niacin.
There has been growing demand for supplements that can boost NAD+ levels in recent years and NA is one of them. The body uses it to synthesise NAD+ through the Preiss-Handler pathway, creating new NAD+ molecules for use by cells. As the new NAD+ is consumed it then enters the body’s normal recycling pathways. NA’s ability to improve the concentration of NAD+ available to cells makes it a credible way to improve the efficiency of cell metabolism among other things. When taken as a supplemental NAD+ precursor, NA can provide significant benefits to health and other biological processes.
Type of NAD+ Precursors
Vitamin B3 has been demonstrated as an effective NAD+ precursor in several studies. Vitam B3 exists in several forms which despite all being the same fundamental chemical, they are not created equal. To fully understand the value of each we need to discuss them. The most common NAD+ precursors are:
Nicotinamide Riboside (NR) – Is widely accepted as an NAD+ precursor supplement and is the most common NAD+ precursor supplement in commercial use. NR has been a focal point of previous NAD+ studies, it has been used to effectively demonstrate the benefits of using supplemental NAD+ precursors to raise depleted NAD+ levels in the human body. However, despite its common use and wide acceptance, NR has a potentially serious side effect. A 2017 study by Airhart found that high NR doses could significantly reduce blood count, notably decreasing both hemoglobin and hematocrit in healthy subjects. This effect was linked to NR itself and not as a result of artificially increasing NAD+ levels.
Niacinamide (NAM) – NAM has been recognised to deliver similar benefits to NR in clinical trials regarding its efficacy in increasing NAD+ levels. However, at high doses such as those required to notably increase NAD+ levels, NAM can impede Sirtuin proteins and disrupt the NRK1 and NRK2 genes. These side effects outweigh any of the potential benefits of taking NAM as an NAD+ precursor supplement.
Niacin (NA) – Unlike other NAD+ precursors supplements that often lack human trials, NA has demonstrated several extremely beneficial effects when being used as an NAD+ precursor supplement in human test subjects. In addition to human testing, NA has previously and continues to demonstrate promising results in tests on animals. Besides its many benefits, NA has minimal significant side effects as noted with other NAD+ precursors which makes it the preferential supplement for increasing NAD+ levels in humans.
So How Good is Niacin?
A recent human trial of NA as a supplementary NAD+ precursor for patients with severe NAD+ deficiency showed remarkable improvements when compared to control subjects. These tests demonstrated significant increases in NAD+ levels within the body, back to the same as their healthy controls. These NAD+ increases correlated directly with increased muscle mass and increased energy levels. Further, several test subjects reported improved sleep, better overall mood and quality of life, and decreased muscle soreness and muscle cramps after intense exercise.
Increased whole blood NAD+ levels in patients 8.2-fold, from severely depleted levels back into a healthy range. Results persisted well after intense use of NA supplementation ceased.
Muscle NAD+ content increased by between 1.3 and 2.3 fold. Similar to blood NAD+ levels, these levels remained consistently elevated after the intense course of treatment was ceased.
Substantially increased muscle mass. Abdominal and back muscles increased in mass 10-fold and 2-fold respectively. Upper extremities such as shoulders and arms increased in muscle mass by 2.5-fold and lower extremities by only 1.1-fold. The reduced increase in muscle mass of lower extremities could be explained by the higher use of lower body muscles for daily activity, meaning their mass was already closer to a healthy range.
The subjects of the test were all mitochondrial myopathy patients, the test had further promising effects that require further study. Most notably, the study suggests that in addition to restoring NAD+ levels and metabolic and functional capacity back to normal, early intervention in the disease process by way of NAD+ supplementation could bypass the primary cause of the disease process. This has also been demonstrated in animal studies in 2014 showing that restoring NAD+ levels rescued both metabolic function and reduced disease signs.
Pros and Cons of Increasing NAD+ Levels With NA
We have discussed how good quality supplemental NAD+ precursors can help to increase and maintain NAD+ levels. We have also covered that this is relevant because NAD+ is critical to healthy cell function and metabolism. Now, let’s look at the main ways that healthy NAD+ impact our health:
- Prevent Age-related Memory Loss
NAD+ is required for DNA repair and neural stress tolerance. As a result, it helps memory enhancement and slows age-related memory decline. According to a recent animal study, researchers created a strain of mice with traits that mimicked human age-related memory impairment, then added an NAD+ precursor supplement to their drinking water for three months to raise NAD+ levels.
According to researchers, the NAD+ treated mice experienced reduced DNA damage, higher neuroplasticity, enhanced synthesis of new neurons, and lower levels of neuronal damage across this time span compared to the control group. This study demonstrated that NAD+ precursors can be used as anti-aging supplements safely and with great effect.
- Strength And Endurance
Muscle function and strength deteriorate with age, this is one of the most prolific and recognised side effects of aging. Recent animal studies have shown that taking an NAD+ precursor supplement can increase muscle density and activity to healthy levels.
In this study, scientists altered laboratory mice to produce only 15% of the muscular NAD+ levels that healthy mice typically have. The muscular strength and endurance of these mice were then tested and showed severely reduced performance compared to unaltered mice. The mice were then given NAD+ precursor enriched water for 1 week. After this week the mice were retested and their exercise capacity was found to be restored to that of a typical, unaltered mouse.
- Counteract High-Fat Diets And Help In Weight Management
High-fat diets are associated with weight gain, reduced energy levels, and difficulty maintaining a healthy lifestyle. Research on animals has shown that mice on high-fat diets given an NAD+ precursor supplement gained 60% less weight than mice on the same diet who were not given the supplement.
In addition to the most obvious benefits of reduced weight gain, the mice who were given NAD+ precursor supplements were also more energetic. The researchers concluded that this was due to improved oxidative metabolisms owing to the increased activation of the sirtuins SIRT1 and SIRT3.
- Side Effects
The primary reason that many supplement manufacturers choose not to use NA in their NAD+ precursor supplements is its visible side effects. While NAM and NR can both have serious negative effects, these effects do not have any obvious, visible manifestation; this makes them ‘marketing friendly’.
NA’s main side effect is known as “niacin flush”. After high doses of NA users sometimes exhibit a slightly increased temperature and redness of the face or limbs. This is usually considered to be a negative side effect, but it is little more than a superficial sign of the Niacin taking effect.
This flushing that sometimes accompanies high Niacin doses is indicative of its rapid beneficial effects. Niacin flushing is a result of increased blood flow. Increased blood flow is desirable because NAD+ is transported to the cells in the bloodstream, plus increased circulation provides more oxygen and nutrients to the cells where it’s needed most.
NAD+ is a critical resource for maintaining healthy cell function, improving metabolic processes, and decreasing age-related diseases in the human body. NAD+ levels naturally decrease with age and this leads to reduced NAD+ related function, including lower energy levels, increased weight gain, and decreased muscle health. Taking supplemental NAD+ precursors has been demonstrated to increase NAD+ in the body back to healthy levels which can reduce and reverse many of the health issues associated with depleted NAD+ levels.
While there are several different NAD+ precursors with varying degrees of effectiveness increasing the body’s NAD+ levels, NA can be considered to be superior to both NR and NAM. NA provides more significant improvements in NAD+ levels than NR, making it preferable of the two. NAM has other negative side effects such as decreased Sirtuin activation and impeded activity of NRK1 and NRK2 genes which makes it unfavourable as an NAD+ precursor supplement. This leaves NA the clear leader as both an effective and safe NAD+ precursor supplement.
Coronary drug project: experience with niacin. Coronary Drug Project Research Group (1991). Berge KG, Canner PL. Eur J Clin Pharmacol. 1991;40 Suppl 1:S49-51.
Pirinen et al. (2020). Niacin Cures Systemic NAD + Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab. 2020 Jun 2;31(6):1078-1090.e5. doi: 10.1016/j.cmet.2020.04.008. Epub 2020 May 7.
Dollerup et al. (2020). Nicotinamide Riboside Does Not Alter Mitochondrial Respiration, Content or Morphology in Skeletal Muscle From Obese and Insulin-Resistant Men. J Physiol. 2020 Feb;598(4):731-754. doi: 10.1113/JP278752. Epub 2019 Dec 26.
Irie et al. (2020). Effect of Oral Administration of Nicotinamide Mononucleotide on Clinical Parameters and Nicotinamide Metabolite Levels in Healthy Japanese Men. Endocr J. 2020 Feb 28;67(2):153-160. doi: 10.1507/endocrj.EJ19-0313. Epub 2019 Nov 2.
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