> 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.
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.
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.
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.
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.
There are any number of suppliers other than the sole sanctioned one. Search Alibaba. Assume you will pay a fraction of what you'd pay the sanctioned suppliers, but you will also have to run a sample via a LC-MS analysis to see that you are in fact getting what you think you are getting. This is all pretty easy to arrange, and works for just about any well known compound, peptide, etc.
If you are willing to do that, one would hope that you are also willing to (a) actually assess the results with the more robust quantified self metrics, rather than just hoping and feeling, as so many people do, and (b) take full responsibility for any harms or legal issues you cause yourself in the course of experimenting, as so few people do.
The detailed guides section here contains a couple of posts that walk through this process for a couple of other items, but the same general outline applies in exactly the same way:
$100-150 to run a sample through LC-MS via any one of dozens of small laboratory groups. Most are willing to explain things to a newcomer who is working his or her way through learning the ropes.
a) surprised that processes that seemed futuristic or industrial are available to the average person at a reasonable price
or
b) surprised that others are surprised
I operate a 4kW laser cutter set up to cut metal. Once new customers realise how much product the machine can put out in an hour they understand that it isn't an expensive service, and that it is in fact almost always cheaper to have an item laser cut rather than do it themselves using any of the tools they have in their workshop.
You can't get in bulk. Chromadex stopped all licensing of its patent so you can only buy it from them at $40/m. Chromadex is exploring FDA approval for certain medical conditions so it will be interesting to see if they keep it on the retail market or it becomes prescription only.
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.
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.
I had no idea about this before taking it. I popped some before going to the store. Thought I was about to crap myself then started getting super itchy. Had to rush home and by then my entire body was lobster red lol
"Among "salvageable precursors" (i.e., Na, Nam, NR), a lot of focus is on NR these days because apparently it activates the "anti-aging" sirtuin genes at high concentrations too compared to Na and Nam which only activate those "longevity" genes only at small concentrations and deactivate them at higher concentrations."
I've been taking Niagen for a couple of months, and I can say that for me it feels much better than niacin or niacinamide. I don't know why (perhaps I have some niacin metabolism problem, or the niacin interferes with some other impaired process such as the methylation cycle).
Also there seems to be some synergy between Niagen and resveratrol and pterostilbene that I can clearly notice. Foods that work well with Niagen are raisin(-bread) and olive oil. Of course, ymmv.
That's interesting. Glad that you are experimenting! Everyone is so different that experimenting is the only way to find out what works and what doesn't for anyone :). Just curious, what other supplements did you find working out for you?
I have read pieces on NR that claim NR is better at "activating" sirtuin production compared with niacin. Is this a load of baloney? Or is NR really different in its effect?
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.
> 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.
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.
> 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.
I've been doing it for two years, and there are solutions to those problems. It's cheaper and faster to eat healthily and restrict calories than to cook a typical US diet -- it just requires a different perspective.
I wish I weren't busy at the moment, so I could build a website about how to manage it.
A few quick ideas from my experiments are below. I'm not a doctor so these aren't recommendations -- just things that I've experimented with.
It requires a change in perspective. A quote I like is, "food is not a recreational drug." Food is fuel for a fermentation tank (digestive system). If you want the machine to run well, figure out what creates ideal fermentation environment. (Watch out for things like sugars and flours.)
I do meal prep by steaming a lot of vegetables in advance[1] and storing them in containers in the refrigerator. Then I can quickly make a variety of meals by combining the vegetables in various ways. Legume (bean, lentil, split pea) and vegetable soups are also good to have on hand at all times. Tahini is a base for a good sauce. I think 2 tbsp will provide about 10% of daily required calcium for most people.
When out of the house, I bring along some chunks of raw red cabbage and raw broccoli.[2] They are cheap, filling, and actually pretty good, especially when you're hungry. I think it's okay to skip meals when healthy food isn't available. Restaurants can also usually provide steamed, plain vegetables on request, if you're eating out with people.
Drink a quart of cold water before starting breakfast and sufficient water throughout the day.
If you need to reduce calories, you can make a cutoff time for eating -- like 4, 5, or 6 pm. That also provides 14-16+ hours of fasting per day to rest the digestive system. Another way to do it is to have reduced calorie days, like on the 5:2 diet.
When reducing calories I focus on high-nutrient foods. My main staple is steamed vegetables. I'd recommend becoming very familiar with different kinds of vegetables and how to cook them (steaming and/or adding to soups). A bookstore would probably have a selection of vegetable encyclopedia-type books.
If it seems hard to maintain a healthy diet, it's still easier than being sick. I went from 215 pounds to 145 pounds, hovering around 150.
Even if you don't reduce calories significantly, a diet focused on vegetables is probably going to have great long-term benefits, including life extension.
If you're in the Bay Area, and want to talk about ideas, you can come to one of our programming meetups.[3] I like to exchange ideas with other people who experiment with food. Or send me an email (josh@codeselfstudy.com), and I'll invite you to a place where I've posted more information about the experiments.
> When out of the house, I bring along some chunks of raw red cabbage and raw broccoli.[2] They are cheap, filling, and actually pretty good
They might taste good (I like nicely cooked and seasoned veg) and be cheap... but "filling"? I absolutely do not find veg filling. More filling that something high in high-GI carbs, sure, since you're not going to have a spike and sharp drop in blood glucose levels signalling hunger, but protein and fat are a lot more filling that veg.
A good example is eggs, which are amazingly filling, cheap, quick to cook, versatile, and only around 150 calories each - and I feel full for at least 5 hours after eating just two of them.
If you do some calorie restriction, raw cabbage will probably be filling. I've been doing it for two years and vegetables are very filling under the right conditions.
I think it's worth eating some cruciferous vegetables raw for additional health benefits.
Compliance for CR is near impossible though. I'm a believer in it but am still 10 pounds overweight. It won't work for everyone, obviously (because so many of us are overweight).
It's not impossible. Look at the CR experiments like CALERIE. Dropout is something like 10-20%, similar to intermittent fasting or other kinds of diets.
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.
"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?
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.
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.
Tangentially related to the safety of niacin, for most people niacin/B3 is relatively inert and used by the body. In fact, if you don't get enough of it, you fall in danger of having pellagra [1].
If I eat it, I'm guaranteed to get an ocular (ophthalmic) migraine.
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.
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.
These numbers include losses and waste. In the most extreme case the US could be wasting a third of their food, while achieving the same intake. So these numbers imply very little about actual calorie intake.
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.
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.
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.
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
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?
>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."
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.
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.
One of my pet peeves is journalists who don't understand what a watt is. I frequently see statements like "The plant will produce 50MW, enough to power 40,000 homes for a year."
As long as you're adjusting the title, I'll point out that the study does not actually demonstrate that the effects on aging are similar. Just that taking the pill creates a metabolite that might possibly have an effect on aging.
> 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.