Highlights:
- Niacin supplementation boosts NAD which is a coenzyme central to cellular energy metabolism
- NAD levels decline with age, so boosting NAD with supplements is thought to be helpful for the optimal functioning of the many cellular repair enzymes
- The three most widely used NAD boosting supplements are Niacin, NMN and NR
- Niacin has the longest history of safe supplementation
The next supplement on our list is niacin (aka Vitamin B3 or nicotinic acid). I realize that while there is a lot of interest in NAD+ boosting, it can be somewhat controversial because there are different schools of thought on what supplement to take to optimally boost one’s NAD+ level. But as per usual, I will dive into the clinical evidence and tell you what I personally do.
The three main supplements that people take as precursors for boosting NAD+ are nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and niacin.
The biology:
I’ll keep this short but a bit of biology is helpful here to set the context. NMN, which has been advocated by David Sinclair, is an NAD+ precursor with a polar phosphate group attached to it. So it cannot get into the cell unless it is ferried across the cell membrane by a receptor or stripped of its phosphate group which converts it into NR. The thinking is that it is first converted into NR and then it can freely enter the cell.
NR, can enter the cell and gets converted into NAD+ through a two-step process. The first step involves conversion of NR into NMN inside the cell, which then gets converted into NAD+. Charles Brenner and his company Chromadex are big proponents of NR.
Niacin, in contrast, makes NAD+ through an entirely different pathway that does not have NR or NMN as its intermediates.
Clinical evidence:
Here it is worth briefly comparing the clinical evidence available for NR, NMN and Niacin supplementation for boosting NAD+. Note that there have been more NR clinical trials than NMN or Niacin, because Chromadex, the manufacturer of NR sold under the brand name Tru Niagen, has been funding clinical trials for its product. In contrast, neither NMN nor Niacin have similar corporate backing. The net result is far fewer NMN and Niacin human clinical trials.
The one recent NMN trial that has generated much excitement, a group of post-menopausal women with prediabetes were given 250mg/day of NMN for 10 weeks (https://alivebyscience.com/first-randomized-clinical-trial-nmn-increases-muscle-insulin-sensitivity-in-prediabetic-women/). This led to higher NAD+ levels in the blood and higher levels of NAD+ metabolites in skeletal muscle. Notably, insulin sensitivity improved, but only in skeletal muscle and not in other tissues.
One of the informative NR trials (https://www.sciencedirect.com/science/article/pii/S2211124719309404) tested 12 elderly men between 70-80 years of age, with 1gram/day of NR for 21 days. When their skeletal muscles and blood cells were tested, they found higher levels of NAD+ metabolites as a sign of elevated NAD+ production. But this did not increase muscle mitochondria levels, grip strength or muscle bioenergetics. In another NR study (https://academic.oup.com/ajcn/article/108/2/343/5051210), 20 healthy obese men aged 30 and 70 were given a daily oral dose of 2 grams of this drug. While there was a substantial increase in NAD+ metabolites, this study also failed to show functional improvements such as insulin sensitivity, energy expenditure, body mass, lean mass etc.
This brings us to the only human clinical trial for Niacin (https://www.sciencedirect.com/science/article/pii/S155041312030190X) that has tested NAD+ levels or its metabolites. Here 5 patients with a condition called mitochondrial myopathy where given an increasing dose of upto 1000 mg/day for 10 months. The patients’ blood NAD+ levels increased upto 8 folds during the course of the treatment while muscle NAD+ levels increased to the level of the healthy control subjects. Muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolites shifted towards normal and liver fat content decreased as much as 50%.
Safety:
Taking Niacin is not risk free. The trouble with Niacin is that it leads to Niacin flush, a temporary discomfort caused by the production of prostaglandins. While this can be uncomfortable, it tends to go away with time. In addition, folks with angina, diabetes, kidney disease, liver disease or gallbladder disease and allergies should proceed with caution. WebMD has a good summary of the possible contraindications and interactions (https://www.webmd.com/vitamins/ai/ingredientmono-924/niacin-and-niacinamide-vitamin-b3).
Supplementation:
In order to avoid the flush, some folks take an extended release (ER) version of Niacin which releases over a few (~4) hours. Please note that this is not the sustained release (SR) version which releases over an even longer period and has been associated with liver damage. Personally, I have been taking the immediate release tablets, in two doses of 200 mg each with food. I find that taking it with food reduces flushing by slowing down the absorption. I am gradually working up to eventually taking 500 mg twice a day.
What I take:
Based on the data I have decided to take Niacin. First and foremost, I feel that Niacin is safer with a far longer history of supplementation. Second, NR and NMN don’t boost NAD+ substantially more than Niacin. While the study was done in mitochondrial myopathy patients, the improvements, in both, NAD+ levels and functional parameters were impressive. In fact NAD+ and its metabolite levels increased in healthy volunteers (controls) as well. Lastly, the cost of Niacin is much lower than either NR or NMN.