Blog 19 The First steps in Human Trials with Nicotinamide Riboside (a form of Vitamin B3) By award-winning author and scientist Mark Kingston Levin PhD
Figure 1. The first steps in Human trials is to demonstrate that the drug in question in not toxic to human. Second does it boost NAD+ levels in humans? The answers is Yes.
The steps has essentially been done by Charles Brenner and his team so that the next step is to demonstrate efficacy in humans not just increase levels of NAD+.
The first controlled clinical trial of nicotinamide riboside (NR), although small it has shown that the compound is safe for most humans; however, larger scale studies will be necessary. Dr Brenner of the University of Iowa has identified NAAD a biomarker to follow the NAD+’s cellular energy production.
Experiments on mice have shown that boosting the levels of this cell metabolite known as NAD+—can produce multiple health benefits, including resistance to weight gain, improved control of blood sugar and cholesterol, reduced nerve damage, and longer lifespan in mice and lower animals.
In most all animals and human beings, the levels of NAD+ dramatical; drops as we age. Several papers by David Sinclair at Harvard have demonstrated in mice that the loss of this metabolite is a key factor in aging and health decline.
These findings in animal studies have spurred people to take commercially available NR supplements designed to boost NAD+. However, these over-the-counter supplements have not undergone clinical trials to see if they decrease or reverse aging in people; however, preliminary short-term studies indicate NAD+ plus level rise in human on a doses of 300 mg twice a day or total 1 gram per day. Millions, like myself who have terminal disease are not waiting for the test results. They are purchasing Niagen band and other NR supplements.
The new research, reported October 10, 2016 in the journal Nature Communications, was led by Charles Brenner, PhD, professor and Roy J. Carver Chair of Biochemistry at the University of Iowa Carver College of Medicine in collaboration with colleagues at Queens University Belfast and ChromaDex Corp. (NASDAQ: CDXC), which provided the NR used in the trial. Brenner works for ChromaDex as a consultant introducing a possible conflict of interest. Similar conflicts are there at Harvard and many other institutions and researchers as well. Dr Brenner is co-founder and Chief Scientific Adviser of ProHealthspan, which sells NR supplements under the trade name Tru NIAGEN®. Dr David Sinclair is co-founder of seven biotech companies. There are billions to be made in the anti-aging business.
The human trial involved just six men and six women, all healthy. Each participant received single oral doses of 100 mg, 300 mg, or 1,000 mg of NR in a different sequence with a seven-day gap between doses. After each dose, blood and urine samples were collected and analyzed by Brenner’s lab to measure various NAD+ metabolites in a process called metabolomics. The trial showed that the NR vitamin increased NAD+ metabolism by amounts directly proportional to the dose. Results today show no serious side effects at any of these doses tested. What dose are desperate people with serious disease taking? I am starting with one gram a day.
Figure 2. The magic molecule of NR sold as Niagen and TRU NIAGEN.
“This trial shows that oral NR safely boosts human NAD+ metabolism,” Brenner says. “We are excited because everything we are learning from animal systems indicates that the effectiveness of NR depends on preserving and/or boosting NAD+ and related compounds in the face of metabolic stresses. Because the levels of supplementation in mice that produce beneficial effects are achievable in people, it appears than health benefits of NR will be translatable to humans safely.”
The next step after Dr. Charles human trails is the University of Colorado Study just out. Please see the reference below:
“Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults”
By Christopher R. Martens, Blair A. Denman, Melissa R. Mazzo, Michael L. Armstrong, Nichole Reisdorph, Matthew B. McQueen, Michel Chonchol & Douglas R. Seals. Please see
Nature Communications, volume 9, Article number: 1286 (2018)
doi:10.1038/s41467-018-03421-7 The paper to see is now available online.
Results show a six months trail of positive NAD+ levels in blood of adult humans. Great news but we need much more. We need to measure the health impact of very large groups of the population over very long times. This is a very important breakthrough. Congratulations to Dr. Sinclair and his associates.
We need to continue and expand the studies and examine the effect of longer duration NR supplementation on NAD+ metabolism in healthy adults. Congratulation to Dr Brenner and his colleagues at University of Iowa. Brenner also has plans to test the effects of NR in people with diseases and health conditions, including elevated cholesterol, obesity and diabetes, and people at risk for chemotherapeutic peripheral neuropathy.
In 2004, a pilot human study on Dr. Brenner began before the clinical trial. He discovered that NR is a natural chemical found in milk. He believes humans will convert NR to NAD+ just as mice do. Ten year of research on NR metabolic pathways and health effects in mice and rats had convinced him that NR supplementation holds great promise to improve human health and wellness, which is yet to be proven.
Following University permission, Dr. Brenner conducted experiments, for example, he took 1 gram of NR dose a day for seven days. His team analyzed blood and urine samples using mass spectrometry. The experiment showed that Brenner’s blood NAD+ increased by about 2.7 times.
Dr. Brenner’s team measured an increase in a 45 time increase in the metabolite NAAD a possible biomarker.
“While this was unexpected, I thought it might be useful,” Brenner says. “NAD+ is an abundant metabolite and it is sometimes hard to see the needle move on levels of abundant metabolites. But when you can look at a low-abundance metabolite that goes from undetectable to easily detectable, there is a great signal to noise ratio, meaning that NAAD levels could be a useful biomarker for tracking increases in NAD+ in human trials.”
“Now that we have demonstrated safety in this small clinical trial, we are in a position to find out if the health benefits that we have seen in animals can be reproduced in people,” says Brenner, who also is co-director of the Obesity Research and Education Initiative, professor of internal medicine, and a member of the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa.
In addition to Brenner, the Iowa based team included lead study author Samuel Trammell, Mark Schmidt, Benjamin Weidemann, Zhonggang Li, and E. Dale Abel at the UI Carver College of Medicine; Philip Redpath and Marie Migaud at Queens University Belfast; Frank Jaksch at ChromaDex in Irvine, Calif, and Ryan Dellinger, formerly at ChromaDex.
The research was funded in part by the National Institutes of Health, the Biotechnology and Biological Sciences Research Council, the Roy J. Carver Trust, and ChromaDex.
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Dr. Levin was born and grew up in Vermont with many winters spent in Florida as a child. As a teenager he wrote poetry, served as a lifeguard and played football. He currently enjoys sailing, exploring underwater caves, snorkeling, writing science fiction and other pursuits. After working on the Apollo and Mars projects, he returned to school to study under Nobel Laureate Paul Dirac, obtaining his PhD in 2.5 years. Dr. Levin founded two companies and served the science policy apparatus in President Ford’s administration. He has been published over 44 times in scientific literature and was awarded over 32 US patents. The science fiction writer is now emerging with his first work, a trilogy entitled 30th Century. The first award-winning book, 30th Century: Escape, is currently available on Amazon. Book two in the series, 30th Century: Revived, is now on Amazon, Barnes and Noble as well as many other retailers.