
Nicotinamide riboside effects on aging similar to caloric restriction - Selfcommit
https://www.colorado.edu/today/2018/03/28/pill-staves-aging-its-horizon
======
johnchristopher
I like that comment from a few days ago
[https://news.ycombinator.com/item?id=16675412](https://news.ycombinator.com/item?id=16675412)

> Go look at the studies showing resistance training to be pretty effective in
> seniors before getting excited about NAD+ boosters. The resistance training
> is probably cheaper and better. One still has studies such as the one
> showing that dietary nicotinamide doesn't do a great deal in mice [3] - like
> sirtuin manipulations, it helps fat mice a little, but is distinctly
> unimpressive otherwise.

> Remember that calorie restriction extends life by 40% in mice, but probably
> five years or less in humans - the effects of all these stress response
> related mechanisms of metabolic manipulation work through a few overlapping
> core processes, and scale down with species longevity. That's why I see them
> as a dead end in comparison to other strategies.

~~~
loeg
I'd take 5 extra QALYs any day.

~~~
nothrabannosir
Ironically, the Q stands for Quality. If the reports on calorie restricted
diets are to be believed, that’s not an appropriate descriptor anymore.

~~~
loeg
Not ironic — that is exactly why I said QALYs and not just years.

~~~
nothrabannosir
Unless I misunderstand QALY, wouldn't n+5 years of misery not necessarily
equal n years of actual quality life? assuming a base quality of 0 < _k_ ≤ 1
with _n_ years, and a calorie restricted life at quality 0 < _k '_ < _k_ with
_n_ +5, surely you'd end up at _k_ * _n_ QALYs for a normal life, and _k '_ *
( _n_ \+ 5) for a calorie restricted one? Which might very well be lower given
how large _n_ is and how much smaller _k '_ is than _k_.

Concretely: 85 years of misery is not 5 QALYs more than 80y of normal life.

Or am I missing your point, here?

~~~
derefr
Yes, you are missing their point: they meant that they'd be happy to do
something that resulted in five additional QALYs, which this is likely not.

------
lvs
OK, the headline and press release basically have nothing to do with the
underlying paper.

The paper itself is a small sample size (24) trial that looks at tolerance.
There are no statistically significant physiological effects of dosing with NR
in the paper. You see a small increase in the levels of various metabolites
that you would expect to see increase after dosing. They only look at
cardiovascular effects, and the results are inconclusive at best.

University press offices are doing nobody any favors with this kind of thing.
It has to stop.

[https://www.nature.com/articles/s41467-018-03421-7.pdf](https://www.nature.com/articles/s41467-018-03421-7.pdf)

~~~
gwerbret
This was a Phase 1 study, which means that it was designed exclusively to test
safety and tolerability of the agent. This explains both the small sample size
and the crossover design. I wouldn't expect there to be even tentative
assessment of effect until they run a larger Phase 2 trial. As for the press
office, all it would know (or care) is that this was published in a decent
journal.

~~~
wpietri
If that's what the press office knows, "A pill that staves off aging? It's on
the horizon" is a ridiculously overblown title.

------
deegles
Does anyone know where to get it in bulk form? The commercial stuff I've seen
seems way overpriced.

Also, I'm happy for the disclosure but be wary of potential bias...

> The study was partially funded by grants from the National Institutes of
> Health and the American Federation for Aging Research. ChromaDex, the maker
> of NIAGEN provided supplements and some financial support.

~~~
e9
Just use high quality niacin/nicotinic acid/vitamin-b3. "niacin
supplementation increases cellular nicotinamide adenine dinucleotide (NAD+)
levels"

reference:
[https://examine.com/supplements/vitamin-b3/](https://examine.com/supplements/vitamin-b3/)

~~~
truculation
Yes and be prepared for that 'niacin flush' if you take a 500mg capsule the
first time. Phew. I had to lie down for half an hour.

[https://niacinreviews.com/niacin-max-
flush/](https://niacinreviews.com/niacin-max-flush/)

~~~
VoiceOfWisdom
Beware the niacin flush. Once I took 500mg, after having already been
accustomed to the flush. It hit hard that day though. 15 minutes after taking
the pill, while driving, my vision started to narrow and go black. It felt
like being chocked out. I was rapidly losing consciousness, but was able to
safely pull over to the side of the road. Before completely passing out I was
able to vomit up what was left of the pill. I was able to return home, and
sleep for the rest of the day. This was with a single 500mg pill, after
already being used to the flush.

~~~
mistermann
FWIW, and not sure if this only helps the itching part of the side effect....

[https://www.leaf.tv/articles/how-to-relieve-an-itch-from-
nia...](https://www.leaf.tv/articles/how-to-relieve-an-itch-from-niacin)

Drink plenty of water. According to Dr. William Davis, a cardiologist from
Wisconsin, ingest 2 8-oz. glasses of water immediately after the itching
sensation begins. According to Dr. Davis, this quick task relieves the flush
and itching symptoms in more than 90 percent of instances.

Take a 325mg table of uncoated aspirin; according to Dr. Davis, this can also
alleviate the itching and burning.

------
JoshMnem
I think calorie restriction is a more interesting idea, because it forces you
to think about eating high-nutrient foods. The first things I did were to
eliminate sugars and other processed ingredients, including all flours.

Continuing to eat junk and assuming that pills and supplements will compensate
for that is probably not a good idea.

~~~
dmix
From the article:

> From a public health perspective [restricting calories] would be impractical
> for many and dangerous for some.

Regardless of what's the most optimal solution it's very helpful to have the
option when this isn't an easy/practical option. And having tried to cut out
sugars and processed foods in my own life, it was certainly not easy and
required a significant monetary and time investment to cook my own meals, and
buy fast-expiring produce.

It doesn't have to be either/or to reach health goals, as you can mix the two
depending on your particular resources.

~~~
naasking
For whom would calorie restriction be dangerous?

I don't get the time and monetary cost either. You can precook your meals for
a whole week on Sunday night, as long as you don't mind a little repetition.

~~~
nopinsight
For the elderly and perhaps others also, too little insulation means a higher
chance of accidents (falls etc.) turning fatal.

It might be quite hard to consume a sufficient amount of certain nutrients
like Calcium on caloric restricted diet as well.

------
YeGoblynQueenne
24 people and six weeks? That is a very small number of people and the time is
not nearly long enough to demonstrate anything like an extension of lifespan.

------
epmaybe
"We are not able to make any definitive claims that this compound is safe..."

Is this quote taken out of context? Because I thought the first step of any
sort of human trial of a drug is to determine its safety. Intuitively I can't
see how NR would be any different safety-wise than niacin (vitamin b3), but
more clarification would be nice. Anyone who has read the paper willing to
chime in?

~~~
marshray
It's fundamentally the responsibility of the FDA to regulate "definitive
claims that a compound is safe", whereas the standard for approval for use in
a clinical trial is a bit different.

~~~
toufka
And this is a general issue with prophylactic or anti-aging style 'drugs'.
Demonstrating a compound is safe enough to not cause undue harm while helping
to rid the body of an accute ailment is a very different kind of 'safe' than
something one might be expected to take every day for years.

------
blunte
As a min/max gamer, I have to ask: do these stack? (nicotinamide riboside AND
caloric restriction)

But I do disagree with the article that caloric restriction is impractical or
dangerous - at least for "rich" western societies that already consume 50%+
more than their healthier eastern counterparts.

~~~
jimrandomh
> consume 50%+ more than their healthier eastern counterparts

That's not true.
[https://en.wikipedia.org/wiki/List_of_countries_by_food_ener...](https://en.wikipedia.org/wiki/List_of_countries_by_food_energy_intake)

~~~
blunte
I'm sorry, 50% is higher than actual. But still, is 3750 for US vs 2550 for
Indonesia (about the same population), or 2800 for Japan, or 2990 for China
any indication of a significant caloric intake difference?

Further, the type and quality of the food is likely much lower for the US
group consider just the relative carbonated, sugared beverage.

~~~
allthenews
How much of that relates to the average body size? I imagine smaller people
eat less.

~~~
Maybestring
I hypothesise a feedback loop by which people that eat more grow in size. I
have conducted some experiments on myself which are consistent with this
theory.

~~~
p0wn
Average male height is 5'2" in Indonesia. The US is 5'9". How has your
feedback loop of eating more helped grow and shrink your vertical height?

~~~
ccho
I assumed radial growth

------
m3kw9
I feel the body could sense some type of contradiction in that it seems like
you are in caloric restriction, but you are really not. The could cause
unknown long term effects.

------
jondiggsit
Is this the same product that Elysium Health sells?

Also, the company ChromaDex seems to have an exclusive right to sell the
compound. Anyone think there's an upside to the stock?

~~~
pwnage12
Yes, it is: [https://www.elysiumhealth.com/supplement-
facts](https://www.elysiumhealth.com/supplement-facts)

Highly doubt there's an exclusive right to sell a compound like this. I know
there are multiple suppliers so doesn't seem to be any patents involved.

------
reasonattlm
What sort of evidence would it take to challenge my assessment of the data to
date that methods of raising NAD+ levels with age, such as nicotinamide
riboside supplementation, are not worth pursuing as a major area of focus in
research and development? Given the history of work in this area of
metabolism, mostly that relating directly to sirtuins and their manipulation,
one has to be a little skeptical. Initially promising (and overhyped) results
in mice went essentially nowhere, or turned out to make the condition of
obesity a little less harmful, while showing little evidence of utility for
healthy individuals.

To answer the question, human data showing meaningful benefits that could not
be achieved via exercise or calorie restriction would be very interesting.
Human data showing some reliable level of reproduction of the benefits of
exercise or calorie restriction without side-effects would be good news for
the present majority who don't put in the effort to stay in shape. Good news
for supplement sellers as well - there is no shortage of people who would pay
rather than exercise or eat less, even if the results were mixed or marginal.

In either case, the cost-benefit analysis runs along the lines of (a) as an
individual, how much it is worth spending on a supplement that can capture a
fraction of the benefits of exercise or calorie restriction, but also (b) is
it worth making this a major focus of the research community, versus the
rejuvenation biotechnology that can achieve far greater gains? I think (b) is
always going to be answered in the negative, for me at least. No calorie
restriction mimetic or exercise mimetic can possibly be as good as functional
SENS repair biotechnologies. They cannot achieve the results produced by
senolytics, or any of the other ways to remove the root causes of aging. If
one looks at NAD+ research as the final stage of sirtuin-related calorie
restriction research as a whole, it has taken as much funding to get here as
it would to completely implement the SENS rejuvenation therapy package in
mice. Yet we know that exercise and calorie restriction cannot add decades to
healthy life, as is possible in principle for repair therapies.

The data here on human nicotinamide riboside supplementation seems promising
in comparison to the results of past sirtuin research, but I'd like to see a
larger study group. If that larger group shows similar results, then maybe
this is worth it for individuals. Either way, it is appreciated that the
authors avoided running a study in overweight individuals - in this part of
the field, that just muddies the waters, given the very different effects of
sirtuin manipulation on thin versus fat animals. Nonetheless, it still appears
to be the case that this is essentially a way to gain some of the beneficial
long-term effects of fitness without putting in the physical effort. I expect
future NAD+ studies and exercise studies in older individuals to converge in
some ways, showing overlapping effects on cellular biochemistry. It is
arguable as to whether taking up exercise, eating less, or artificially
increasing NAD+ levels should be termed rejuvenation. There is a certainly a
sizable grey area at the intersection of repair, compensation, and overriding
regulatory signals that respond to aging.

------
ggm
Eat Vegemite.

~~~
Numberwang
Why?

~~~
petecox
It is marketed as high in Niacin.

~~~
ggm
It's the other B3 not this one btw, and apparently to get close to this dose
you'd be a happy little Vegemite shareholder: it's way above the daily
smearing

------
isoprophlex
There is a very annoying, pervasive typo in the article and in the title on
hn. It's 'nicotinamide'. In chemistry, an omide isn't really a thing.

Edit: and I'll add another sour note... I noticed this now, but how often did
i read a piece of journalism outside my area of expertise with equally lazy
mistakes, without noticing them?

~~~
oakwhiz
>how often did i read a piece of journalism outside my area of expertise with
equally lazy mistakes, without noticing them?

This is often referred to as the "Gell-Mann Amnesia Effect":

"Briefly stated, the Gell-Mann Amnesia effect works as follows. You open the
newspaper to an article on some subject you know well. In Murray’s case,
physics. In mine, show business. You read the article and see the journalist
has absolutely no understanding of either the facts or the issues. Often, the
article is so wrong it actually presents the story backward-reversing cause
and effect. I call these the “wet streets cause rain” stories. Paper’s full of
them. In any case, you read with exasperation or amusement the multiple errors
in a story-and then turn the page to national or international affairs, and
read with renewed interest as if the rest of the newspaper was somehow more
accurate about far-off Palestine than it was about the story you just read.
You turn the page, and forget what you know."

~~~
Confusion
Which should of course not be exaggerated and fully blamed on the reporter.

A reporter not understanding what a physicist explained does not mean they
lack the ability to understand what a policeman or politician told them.

A reporter not being able to explain a theory does not mean they cannot
correctly report on the plain facts of a murder or a policy proposal.

In such cases the risks are inferences drawn from the (lack of) facts, the
reliability of the source (material), etc. Every kind of article requires
scepticism of different aspects. Just ensuring you don't suffer from Gell-Mann
Amnesia is woefully insufficient.

~~~
scarhill
Except it's not just complex scientific subjects they get wrong. If you start
looking for it you'll find it's anything that you know about. I've observed it
in articles on pigeon racing.

Here's the source for the Gell-Mann Amnesia Effect quote:
[https://web.archive.org/web/20061020012137/http://www.cricht...](https://web.archive.org/web/20061020012137/http://www.crichton-
official.com/speeches/speeches_quote03.html)

