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Nicotinomide Riboside Linked To Proxy For Healthier Aging In Pilot Study

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Nicotinomide Riboside Linked To Proxy For Healthier Aging In Pilot Study

"In a small pilot study consume who consumed a natural dietary supplement called nicotinomide riboside (NR) daily showed signs of mimicking caloric restriction, which in mice has been linked to health benefits.

Caloric restriction is a starvation diet. When lower level organisms such as fruit flies, roundworms, rodents are raised on such a diet from birth, slashing of caloric intake by about a third has health benefits and, in some cases, extended lifespan. No humans have done that, it would be a human rights violation to wean a baby on a starvation diet, and claims about benefits in adults who took it up have too many confounders to be anything more than anecdotes. 

In a small pilot study, 12 lean and healthy men and women ages 55 to 79 from the Boulder area were given a placebo for six weeks, then took a 500 mg twice-daily dose of nicotinamide riboside chloride (NIAGEN). Another 12 took nicotinamide riboside for the first six weeks, followed by placebo. The researchers took blood samples and other physiological measurements at the end of each treatment period. They found that the supplement slightly improved blood pressure and arterial health, particularly in those with mild hypertension but what they wanted to find was that 1,000 mg daily of nicotinamide riboside boosted levels of another compound called nicotinamide adenine dinucleotide (NAD+) by 60 percent. NAD+ is required for activation of enzymes called sirtuins, which is hypothesized to be involved in the beneficial effects of calorie restriction. It's involved in a host of metabolic actions throughout the body, and tends to decline with age.

...

The pilot study also found that in 13 participants with elevated blood pressure or stage 1 hypertension (120-139/80-89 mmHg), systolic blood pressure was about 10 points lower after supplementation. A drop of that magnitude could translate to a 25 percent reduction in heart attack risk but this is a pilot study in healthy people, so it should only be considered a viable technique if a company is willing to enter it into clinical trials. Otherwise, it will remain just another supplement for people who want to believe."

https://www.science20.com/news_staff/nicotinomide_riboside_linked_to_proxy_for_healthier_aging_in_pilot_study-240388

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And then, there is this:

"What is the Difference Between NMN and NR? Is it Superior? Nicotinamide Mononucleotide Vs Nicotinamide Riboside

The reason you hear way more about Nicotinamide Riboside (NR) is pretty simple, money and availability.
When the landmark study in 2013 was released, not only is NMN unpatentable due to it being classed as a common compound (like you can't patent air), NMN was also not ready for mass industrial production.

On the other hand, a company called Chromadex had a patented compound that purported to increase NAD+ reliably and jump in to quickly say NR is almost the same thing. Since NR is patented, it could be sold at a much higher mark-up and licenses can be sold to other supplement companies like Elysium, thus the original compound used in both the 2013 and then 2016 compound was swept under.

Of course, initially, people were drawn to NR, especially since it would be commercially available first, however over time more and more people began to suspect that NMN was better or at least it was just as good.

Why sell you NR (Nicotinamide Riboside)? Apart from the high-profit margins gained from being a patented product (unlike NA/NAM/NMN).  NR is 2 steps away from NAD+ , NR first converts INTO NMN before be converting finally to NAD+.

On the other hand NMN converts to NAD+ directly - meaning it is a 1 step process. NMN is closer to NAD+ than NR.

...

It has been suggested that high levels of NAD+ may simply be downregulated, explaining why some people feel amazing effects that disappear in a few weeks. This goes in tandem with the longer term studies which suggested that NAD+ increases are downregulated by homeostasis.

Since NAD+ levels decrease rapidly due to aging, it is likely that supplementing NMN/NR during middle age would raise NAD+ levels to normal and no more.

If this hypothesis is true, then this will be true for both NR and NMN.

Oversupplementation may lead to downregulation of otherwise healthy natural levels of NAD+ thus creating a dependence on exogenous NMN/NR, mean,ing upon sudden withdrawal of NMN/NR NAD+ levels would be far lower than before homeostasis kicks in.
"

https://stardust.bio/article/76/nicotinamide-mononucleotide-nmn-explained-all-research-and-overview

 

Any thoughts?

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NAD+ is an interesting topic,  and, as you know,  there's already been a lot of discussion on it here:

NAD supplement?  By Mechanism   https://www.crsociety.org/topic/11649-nad-supplement/

For me,  there are just too many iffy things about NAD boosting, so I'm keeping away from it for now. (Btw, the small pilot study you cite used a fairly high NR dosage-- 1,000mg/day-- which  is pretty radical,  not too mention costly.)

 

Ex-CR practitioner Brian Delaney  is pretty hot on NAD restoration therapy  (he admits he quit serious CR purely out of vanity--he just couldn't stand  the way his skinny-ass CR'd body looked.)  

See An interview with Brian Delaney starting around 1:01:53 where he discusses various  means of increasing NAD+  levels, including NR supplementation.  

https://www.crsociety.org/topic/16980-an-interview-with-brian-delaney/

 

Edited by Sibiriak

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Sibriak, you are right.

1g is a really high dose, and very profitable to the NR patent holders.

I actually thought the oversupplementation argument made above was interesting and deserves some pondering -- is anyone aware of a long-term study of B-Complex or similar supplementation, which would support or invalidate such line of thinking?

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Sibiriak,

Nice links and insightful comments, as always.  Indeed the supplement industry - perhaps in exaggerated fashion relative to some other sectors - is a microcosm of life: in answer to “why things are they way they are,” at least part of the explanation is often, “follow the money.”

The initial promise of NR was not without reason.  Indeed MR takes NR ( coincidence? I think not!  “Michael Riboside” has a nice ring to it, and “Nicotinamide Rae” may trump that).  He does so with ample caution and qualification though - see  https://www.longecity.org/forum/stacks/stack/122-michaels-tiered-supplement/ .

For my part I have followed the NR story over the past few years and every time I edged closer to seriously considering supplementation, without delay it was followed by another study raising sufficient concern over risk outweighing hypothetical and questionable efficacy - particularly in healthy non-geriatric CR’d individuals.  I have held off.  

As with all things lifestyle, when the preponderance of data changes, I will change with the data.

 

 

Edited by Mechanism

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A few excerpts from David Sinclair's book Lifespan:

Quote

 

Every day I’m asked by members of the public, “Which is the superior molecule: NR or NMN?” We find NMN to be more stable than NR and see some health benefits in mouse experiments that aren’t seen when NR is used. But it’s NR that has been proven to extend the lifespan of mice. NMN is still being tested. So there’s no definitive answer, at least not yet.

...

We also see that NMN is able to restore the fertility of old mice that have had all their eggs killed off by chemotherapy or have gone through “mousopause.” These results, by the way, even though they were done multiple times and reproduced in two different labs by different people, are so controversial that almost no one on the team voted to publish them. I was the exception. They remain unpublished, for now.

...

The ovary is also the first major organ to break down as a result of aging, in humans and animal models alike. What that means in mice is that, instead of waiting for two years for a mouse to reach “old age,” we can start to see and investigate the causes and cures for aging in about 12 months, at the age female mice typically lose their ability to reproduce.
We also have to remember what NMN does: it boosts NAD, and this boosts the activity of the SIRT2 enzyme, a human form of yeast Sir2 found in the cytoplasm. SIRT2, we’ve found, controls the process by which an immature egg divides so that only one copy of the mother’s chromosomes remain in the final egg in order to make way for the father’s chromosomes. Without NMN or additional SIRT2 in old mice, their eggs were toast. Pairs of chromosomes were ripped apart from numerous directions, instead of exactly two. But if the old female mice were pretreated with NMN for a few weeks, their eggs looked pristine, identical to those of young mice.43
All of this is why early indicators of restored ovarian function in humans, anecdotal as they may be, are so fascinating.

...

By the time my mother died in 2014, my father’s health had also begun its seemingly inexorable decline. He had retired at 67 and was in his mid-70s, still fairly active. He liked to travel and garden. But he had passed the type 2 diabetes threshold, was losing his hearing, and his eyes were starting to go bad. He would tire fast. He repeated himself. He was grumpy. He was hardly a picture of exuberant life.
He started taking metformin for his borderline type 2 diabetes. The next year he started taking NMN.
My father has always been a skeptic. But he is also insatiably curious and was fascinated by what he heard from me about what was happening to the mice in my lab. NMN isn’t a regulated substance; it’s available as a supplement. So he tried it out, starting with small doses.
He knew quite well, though, that there are very big differences between mice and humans. At first he would say to me and to anyone else who asked, “Nothing has changed. How would I know?”
So the statement that came about six months into his NMN tryout was telling.
“I don’t want to get carried away,” he said, “but something is happening.”
He was feeling less tired, he told me. Less sore. More mentally aware. “I’m outpacing my friends,” he said. “They’re complaining about feeling old. They can’t even come for bushwalks with me anymore. I’m no longer feeling that way. I don’t have aches or pains. I’m beating much younger people at rowing exercises at the gym.” His doctor, meanwhile, was struck by the fact that his liver enzymes normalized after twenty years of being abnormal.
Upon his next visit to the United States, I noticed that something else was different, something very subtle. It dawned on me: for the first time since my mother’s death, the smile had returned to his face.
These days, he runs around like a teenager. Hiking for six days through wind and snow to reach the peak of the highest mountain in Tasmania. Riding three-wheelers through the Aussie bush. Hunting remote waterfalls in the American West. Zip-line touring through the forest in northern Germany. Whitewater rafting in Montana. Ice cave exploring in Austria.

 

I know Sinclair is often accused of premature and/or excessive enthusiasm for things such as reserveratrol and NR but I think Sinclair profits from sales of NR and not NMN which if true at least removes personal gain from the motivation to hype preliminary findings on NMN.

Here is a Chris Masterjohn video addressing the question of NMN vs NR where he comes down on the side  of NR for now.  But suggests the possibility that they may be equivalent at least for most people, it just isn't sufficiently researched yet.

 

Edited by Todd Allen

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