Nicotinamide Riboside – Niacel – Part 1
This is the first part of four on a new compound to the marketplace. Once 
you’ve had a chance to read and digest them, you will be aware of information only a handful of people, mostly high academic researchers know. The new compound is called nicotinamide riboside. The knowledge of its importance, its patent on manufacturing, and wide array of ongoing research comes to us mostly from MIT, Harvard, and Cornell. With this information you are at the tip of the spear in regards to cutting edge data with numerous implications from obesity, diabetes, neurological conditions, fatigue, high serum lipids, inflammation, cancer, oxidative stress, vascular heath, and more.
The biochemistry is a bit dense, and I’ll try to relay it to you while still doing it justice. It bothers me when someone tells you to “just take something” without giving the biochemical reasons behind their recommendation. I work in the natural/integrative/function medicine industry, as do many others, because we ask “why”. Otherwise, we’d be slinging drugs at you and telling you to come back in a month if you weren’t feeling better for another drug which would most likely mask your symptoms, while not addressing the underlying biochemical reason for your condition. I was tasked with being the science lead on this novel compound by the premier company in the professional supplement (nutraceutical) space, Thorne Research. Given my strong background in the field, which is essentially a field of biochemistry, and my passion for natural medicine, I happily read just about all the information out there on the topic. I am very excited about this molecule. I have read thousands of clinical papers over the years. As a point of reference, in my book “Reduce Your Healthcare Costs Through Natural Medicine” I have almost 1,000 references in it alone. When you consider I probably read two for every one I accepted, that’s a lot of research. I will honestly tell you I’ve not been this excited about anything in our space previously. Nicotinamide riboside (especially when administered with resveratrol) is bigger than fish oil, CoQ10, or any other supplement you can think of, and now I’ll begin to explain why I think so.
Nicotinamide Riboside (NR) is a novel and new ingredient to the professional market. As the name implies, it is a form of niacin with a ribose molecule. As practitioners, we know niacin well, or at least we think we do. We are all accustomed to three forms of niacin. There is nicotinic acid (NA), which has numerous studies which support its use in support of serum lipids, but carries with it the likelihood of flushing, which may or may not be tolerable for the patient. There is inositol hexanicitinate/hexaniacinate (AKA flush-free niacin) which in theory should offer up the same lipid benefits as NA without the flush, but does not, for reasons yet to be elucidated. Lastly there is niacinamide/nicotinamide (NAM) which is yet another theoretical approach to administering niacin, but according to accumulating data, not the wisest choice.
NR is most likely the best option for administering niacin to date, and the reasons for this are more numerous than you could possibly have imagined. NR does not originate from the tryptophan/NA pathway. It is a part of what’s referred to as the salvage pathway (technically NA is a part as well). In order to make enough NAD+, the body must primarily recycle NAM. See figure 1.
As you can see, NAM is a byproduct of NAD+ catabolism. To regenerate NAD from NAM the enzyme nampt adds a phosphate and ribose to NAM, it creates the intermediate nicotinamide mononucleotide (NMN). Nampt is upregulated in times of stress, and is often said to be rate limiting. NMN is not commercially available as an NAD+ precursor, but NR is. NR is phosphorylated by the enzymes nrk 1 and 2. Nrk1 is expressed ubiquitously, while nrk2 is less so.
When NAD+ is catabolized by NAD+ degrading enzymes (which we’ll get to in the next piece) the remnants are a deacetylated protein, 2′-O-acetyl-ADPribose , and NAM. So, NAM is a byproduct, essentially a waste product which inhibits the function of NAD+.
NR is not some radical compound lacking testing and safety. It is a natural intracellular and extracellular component, as well, it exists in the diet, most notably in the whey fraction of milk. NR has a variety of trials over the past number of years, and the interest level and speed of research is accelerating exponentially as the full weight of this molecule is now beginning to be understood. Research is ongoing at top flight institutions as Harvard, MIT, Cornell, and Dartmouth to name a few.
Below is a 7 minute video of Dr Leonard Guarente of MIT, one of the pioneers in this field, and whose prodigy is Dr Dave Sinclair of Sirtris (resveratrol) fame. It’s worth the time, and there are other Guarente and Sinclair videos you can view for a broader understanding.
What they are discussing here is not to be confused with NAD+ as it related to NADH. We all can vaguely recall where NAD+ plugs into say glycolysis or the Krebs cycle to yield NADH which then goes on to the electron transport chain, the site of oxidative phosphorylation. This is a reduction-ATP generating phenomena which is the aerobic source of much of our energy. Although not the bulk of this paper, this is an important piece of the puzzle.
So for those without a science background, very simply the common unit of energy from which our body works is called ATP. You can make ATP from starches and sugars, you can make it from fats, and you can make it from proteins. In the end, all the cycles that degrade these macronutrients make ATP. In the end, there is a good bit of truth about us being compared to a battery like in the Matrix movies.
With age and disease, your ability to make ATP declines. NR (the produce name is called Niacel) is the most efficient way to do this. So purely from a fatigued patient’s point of view, there is marked potential to help increase ones energy, which is probably the most common report I receive from patients and doctors alike. It seems to take days to a week to notice, and the dosing is probably best at two capsules per day.
If you are a healthcare provider of any type (or you just want to learn about the mitochondria), you should watch this very informative presentation by Bob Rountree MD, one of the brightest minds in the integrative medicine space.
Be prepared for a lot more information in the coming pieces. In the meantime, you can always hop onto pubmed.gov, which is where most of the research in the world is housed. In the search field type in nicotinamide ribsoside, and start reading. To make it easier, you may want review articles only as opposed to original research.
Guy Daniels MS MH