2266 replies to this topic

[sthira]

Just a quick anecdote for the record. As I reported here, I had never taken NR until this week. I took one 100 mg per day for 2 days, just as a sort of safety check (LEF brand) because I was planning to use it to mitigate CT scan damage. I didn't really notice anything. On the day of the CT itself, I took 500 mg before and after, for a total of 1 g on that day. The result seems to have been alertness to the point of pain, which only subsided with choline ingestion. I might be misinterpreting the event, but it was unprecedented in my memory, so I thought to report it.

I'm taking a gram a day along with pterostilbene interspersed throughout the day, and have noticed no "alertness to the point of pain." I've noticed nothing.

[resveratrol_guy]

 

Just a quick anecdote for the record. As I reported here, I had never taken NR until this week. I took one 100 mg per day for 2 days, just as a sort of safety check (LEF brand) because I was planning to use it to mitigate CT scan damage. I didn't really notice anything. On the day of the CT itself, I took 500 mg before and after, for a total of 1 g on that day. The result seems to have been alertness to the point of pain, which only subsided with choline ingestion. I might be misinterpreting the event, but it was unprecedented in my memory, so I thought to report it.

I'm taking a gram a day along with pterostilbene interspersed throughout the day, and have noticed no "alertness to the point of pain." I've noticed nothing.

 

 

Thanks for the feedback. Did you start out at a gram a day, or work up to it?

 

It might have been a synergistic effect of the whole regimen, but NR was the only thing in this CT scan stack that was genuinely new, hence my suspicion. I'm also taking about 300 mg/d of pterostilbene, and have done for a long time.

 

I wonder if I experienced something like what happened to Decimus. I did feel great the next day, once I got over the head pain. It seems as though he didn't attempt to rescue himself from the burnout by administering choline. Hmm...

Edited by resveratrol_guy, 31 October 2015 - 04:25 AM.

[sthira]

Just a quick anecdote for the record. As I reported here, I had never taken NR until this week. I took one 100 mg per day for 2 days, just as a sort of safety check (LEF brand) because I was planning to use it to mitigate CT scan damage. I didn't really notice anything. On the day of the CT itself, I took 500 mg before and after, for a total of 1 g on that day. The result seems to have been alertness to the point of pain, which only subsided with choline ingestion. I might be misinterpreting the event, but it was unprecedented in my memory, so I thought to report it.

I'm taking a gram a day along with pterostilbene interspersed throughout the day, and have noticed no "alertness to the point of pain." I've noticed nothing.

Thanks for the feedback. Did you start out at a gram a day, or work up to it?

It might have been a synergistic effect of the whole regimen, but NR was the only thing in this CT scan stack that was genuinely new, hence my suspicion. I'm also taking about 300 mg/d of pterostilbene, and have done for a long time.

I wonder if I experienced something like what happened to Decimus. I did feel great the next day, once I got over the head pain. It seems as though he didn't attempt to rescue himself from the burnout by administering choline. Hmm...

Wow, I'm happy if you're gaining from it, and I wish I did feel something like Decimus reported in your link. But I've felt nothing like that at all. I'm more like the poster responding just after Decimus -- Trance -- who also reports feeling nothing at all.

By this point I've taken a lot of Niagen -- up to two grams a day with pterostilbene. I've been on this lonely quest for about a year or so. I started at 250 mg and have just kept upping it. For me I think I could take a whole bottle and still feel nothing. What am I supposed to feel? Godlike, like Decimus reported, he makes it sound almost like a psychedelic mushroom experience? I'm probably peeing Niagen right out of me, and it's just too expensive to continue taking it if I'm gaining no health benefits. So this is my last try for Niagen. I've several bottles left. I don't really know what I'm supposed to feel, or if I'm supposed to feel anything at all. Too bad we have no community. We're all just sort of individuals, and so grasping in the dark. It's a lonely experience, I wonder about it, this quest... For something...

[Bryan_S]

use it to mitigate CT scan damage.

 

I think this application is very intuitive from what we understand on the DNA damage from X-Ray exposure. We also know that UV damage can also be mitigated with B3. Nice connection.

 

As far as the rest of this conversation the effects are very hard to quantify from our abstract experience.

 

I'm in my mid 50's and do truly feel the physical and mental boost but what exactly is that and is it quantifiable? On the other hand I have inflammatory joint issues and an unsightly skin condition which have booth abated since taking NR, so these are an easier metric for me to gauge. If I discontinue the NR as I've done in the past, I do return to my previous condition and don't feel as mentally alert, focused and fatigue much easier, my severe joint inflammation also resumes. 

 

In my mental capacity I have something less subjective than saying I feel more alert. I work in a TV station and half of my duties are directly reflected in the TV station logs, so there is no way of getting around this. These are performance based tasks and any errors I might make will go out on the air "LIVE" for everyone to see. So being in a position where I'm evaluated against my co-workers on an "error basis" gives me a unique perspective that I'm attuned to in the time frame before starting my NR regiment and after. My error rate was previously low but its now almost non-existent now.

 

If I were a young, fit, athletic individual I don't think I'd have the same perspective because I expect much of what NAD boosting is doing under the hood, on a Sirtuin and PARP level, "which as we all know are NAD dependent enzymes," would fly under the radar of our physical awareness. So these effects are far less quantifiable unless we subjected ourselves to tests in a laboratory environment.

 

So I see effects on conserved mammalian energy pathways which over time should accumulate into meaningful health benefits. For now we'll just have to put our faith in the metabolic biologists who tell us these effects are ubiquitous across all mammalian metabolism. That's my 2 cents for what its worth and these are not easy questions to ponder.

[sthira]

Thanks, Brian. Admittedly it's been your posts, study notices, and gentle pitches that have led me on to try out Niagen. Sinclair's words influenced me, too, although I think he was talking about a different substance.

For me personally, I'm younger stage performer, healthy, athletic, but have a torn knee meniscus which has kept me off the floor for more than a year. I lost my leap, as they say in this business, and it's the result of a split shock absorber. :-( I tried Niagen at ever increasing doses (500 mg in the AM, increasing by 125 mg all day til reaching 2 g) knowing beforehand that chances for healing were zero-percent since the tear is in an avascular zone. But I thought what the hell, I'll try it out anyway, strange things happen sometimes in life and in bodies, and maybe it'll reduce inflammation. But it hasn't reduced joint inflammation, nor have I "felt" the sorts of mental and physical effects you're noting, and it's very expensive even buying it through your longecity discounts. I'm grateful for those discounts, and I'd be really happy if Niagen did anything positive, frankly.

[resveratrol_guy]

@ sthira: I'm not surprised that you're not seeing benefits if you're a young stage performer, presumably in better mitochrondrial health than either Bryan or me. You might try megadose Longvida and see if it relieves your joint pain. I would suspect so. Mesenchymal stem cells would probably help as well, but it's debatable whether it's worth the expense and risk when an ace bandage would at least hold you together.

 

@ Bryan_S: Your error rate metric and skin observations are quite objective and valuable, so thanks for that. I should add that I've noticed something quite odd in my sporadic dosing. It gives me a broadbased mental boost -- visualization, situational awareness, and longterm and shortterm memory -- for about 2 hours after taking a measly 100 mg, which is not to the level of pain that I experienced with 1 g. (I wasn't expecting to be so mentally adept the next day, as I only took it as a radiation shield, so I don't think it's placebo.) So anyway that would suggest that part of my chronic brain fog of the past couple years has been due to mitochondrial deficits.

 

However, this is strangely at odds with my experience with MCT oil. MCT is supposed to boost the cognitive performance of dementia sufferers within a matter of hours. Although it improved my endurance, multiple tablespoons of the stuff never improved my mental function nearly as much as 100 mg of LEF NR.

 

So what does this mean? Let's see... MCT is supposed to supply beta-hydroxybutyrate to my brain mitochondria, allowing me to bypass supposedly-impaired glucose metabolism, resulting in better cognition. But it doesn't really work, suggesting that my glucose pathway is still OK (which would be consistent with my low fasting glucose). But then NR does have a rapid effect -- where even niacin and niacinamide don't -- suggesting that I'm not making enough NAD+ from my glucose.

 

So this sounds like a contradiction, in that my glucose pathway seems fine, but NR noticeably helps me. I don't get it. How could that be, especially when the other B vitamins fail me? What I am missing here (a lot, obviously)?

 

[Bryan_S]

Thanks, Brian. Admittedly it's been your posts, study notices, and gentle pitches that have led me on to try out Niagen. Sinclair's words influenced me, too, although I think he was talking about a different substance.

For me personally, I'm younger stage performer, healthy, athletic, but have a torn knee meniscus which has kept me off the floor for more than a year. I lost my leap, as they say in this business, and it's the result of a split shock absorber. :-( I tried Niagen at ever increasing doses (500 mg in the AM, increasing by 125 mg all day til reaching 2 g) knowing beforehand that chances for healing were zero-percent since the tear is in an avascular zone. But I thought what the hell, I'll try it out anyway, strange things happen sometimes in life and in bodies, and maybe it'll reduce inflammation. But it hasn't reduced joint inflammation, nor have I "felt" the sorts of mental and physical effects you're noting, and it's very expensive even buying it through your longecity discounts. I'm grateful for those discounts, and I'd be really happy if Niagen did anything positive, frankly.

 

Sinclair used nicotinamide mononucleotide (NMN) which NR is converted into before NAD. Closely related is an understatement and he picked a competitive research path to the Charles Brenner studies to generate his results. Its a more complicated, sensitive molecule which is converted to NR at the cell membrane.

 

Keep in mind that most of us who feel the effects are older and the mind isn't immune to the ravages of time.  So when you regain something you've lost you take notice.

 

Been there with a torn knee meniscus myself so I can relate. Mine was the result of a soccer injury and I further aggravated it with long distance running. I had my meniscus removed at the recommendation of my doctor and the swelling eventually abated. This was in the years before micro surgery and today they would have approached it differently.

 

As you suggest the healing potential in the central avascular zone isn't good. It simply isn't well vascularized as it was explained to me, mine was similar. If I had it to do again I don't think NR would have given me the relief I needed, in fact I know so. I would have still opted for the surgical approach. I'm sorry to hear of your discomfort and understand your loss of mobility and I wish you a speedy recovery.

 

The inflammation problems I speak of today aren't even related to that now missing meniscus and its more closely related to arthritis in joints I've re-injured on several occasions. So I have a very different problem.

 

If I were you, I would still use all the traditional sports medical interventions including rest, cold packs, ibuprofen/naproxyn and elevation of the limb until my Doctor could render a satisfactory treatment. Even today with my NR regime I pull out a mega size Chattanooga Cold pack  (11" x 14") from my freezer and elevate the effected limb when I need to. I've learned to live with my joint inflammation and use every tool at my disposal to maintain my mobility. NR is one of those tools and it's helped give me an edge in keeping it in check, but realize I am not apposed to conventional medical practices and over the years I've dropped a lot of money on Orthopedic specialists and will likely see more in my future.

 

So my apologies if you were lead to believe this could be a cure for a torn knee meniscus, no one here would recommend NR over an excepted medical treatment for a mechanical cartilage tear. Even if NR could help speed healing in ideal situations you are talking about a damaged weight bearing meniscus and you are constantly re-injuring the site just by just walking on it. So with all do respect I would recommend seeing an Orthopedic specialist, because these types of injuries, in the area you suggest, rarely heal themselves.

 

So I am a B3 advocate as you suggest but I also understand it isn't a cure all merely an aid. 

Edited by Bryan_S, 01 November 2015 - 06:29 AM.

[Bryan_S]

So this sounds like a contradiction, in that my glucose pathway seems fine, but NR noticeably helps me. I don't get it. How could that be, especially when the other B vitamins fail me? What I am missing here (a lot, obviously)?

 

In the same boat as an old man.

 

NAD, NADH, Nicotinamide and Niacin all fall in the same B3 family with Nicotinamide Riboside. This is how I understand it in a simplified explanation, as youngsters our cells easily recycled the B3 amounts we needed. Our diets also included trace amounts of B3 to keep up with any losses and in our gut tryptophan was produced which could also contribute. Somewhere along the line this NAD+ salvage pathway slowly got down-regulated and the reasons for this aren't exactly well understood yet. With a diminishing NAD pool our Mitochondria also reduced in number. So the aerobic respiratory machinery we rely on slowly reduces in number and with it our overall NAD thru-put capacity. So naturally our anaerobic glucose metabolism steps in to make up the energy difference but its a more toxic energy producing method. Even as youngsters our metabolism steps between the 2 worlds but as we grow older we use the dirty method more often and it carries ROS consequences. NAD boosting is an attempt to reenergize our diminishing aerobic metabolism and higher NAD levels over time have been shown to increase our mitochondrial numbers. You are likely just feeling the temporary NAD boost, as to pain at higher levels you might be noticing something else I can't speculate on.

 

I believe my mental capacity had already suffered, I just wasn't aware, so when the fog began to lift I said WOW and took notice.

Edited by Bryan_S, 01 November 2015 - 07:33 AM.

[sthira]

Thank you both Resveratrol Guy and Bryan, this is all very interesting. I didn't really expect Niagen to help my condition much, but stranger things have happened so thought I'd give it a long, fair try. I'm taking several other compounds to help with the torn cartilage, and Ibuprofen is by far the most effective. Other anti-inflammatories -- I feel like I've tried them all, including large doses of Longvida -- simply are not as effective or predictable as ibuprofen. I don't like the longterm stomach damage I may be causing with ibuprofen, but there's little other choice (beyond RICE) and compressing the area as you both mention. I've also tried acupuncture, TENS, chiropractic procedures, PT (quad strengthening). I had an arthropedic scope, and the surgeon removed half of the precious flesh, and said it would never grow back. I've been following stem cell updates in this arena, but it's evidently still in sheep trials, moving very very slowly, and generalized stem cells seem hit or miss, and as you say way outside my budget. There's no way I can afford some procedure in which hip cells are translocated into knee cells, and expected to stay in the affected area. There are 3D scaffolds currently being studied, then seeded with stem cells, but there hasn't been recent news on this for almost a year now regarding the sheep.

Anyway, sorry for derailing the conversation here, and thank you for the kindness expressed in your posts. I'm happy Niagen is working for some people for some conditions some of the time. Hopefully, newer, more effective, and more fairly priced options will be available near-term. It's a pity that capitalism is in the way, and companies are compelled to gouge sick and hurt people just to buy bigger houses or boats or whatever the hell they need to buy to make themselves feel better at the expense of others. Oops -- I'm ranting...

[resveratrol_guy]

 

So this sounds like a contradiction, in that my glucose pathway seems fine, but NR noticeably helps me. I don't get it. How could that be, especially when the other B vitamins fail me? What I am missing here (a lot, obviously)?

 

In the same boat as an old man.

 

NAD, NADH, Nicotinamide and Niacin all fall in the same B3 family with Nicotinamide Riboside. This is how I understand it in a simplified explanation, as youngsters our cells easily recycled the B3 amounts we needed. Our diets also included trace amounts of B3 to keep up with any losses and in our gut tryptophan was produced which could also contribute. Somewhere along the line this NAD+ salvage pathway slowly got down-regulated and the reasons for this aren't exactly well understood yet. With a diminishing NAD pool our Mitochondria also reduced in number. So the aerobic respiratory machinery we rely on slowly reduces in number and with it our overall NAD thru-put capacity. So naturally our anaerobic glucose metabolism steps in to make up the energy difference but its a more toxic energy producing method. Even as youngsters our metabolism steps between the 2 worlds but as we grow older we use the dirty method more often and it carries ROS consequences. NAD boosting is an attempt to reenergize our diminishing aerobic metabolism and higher NAD levels over time have been shown to increase our mitochondrial numbers. You are likely just feeling the temporary NAD boost, as to pain at higher levels you might be noticing something else I can't speculate on.

 

I believe my mental capacity had already suffered, I just wasn't aware, so when the fog began to lift I said WOW and took notice.

 

 

So let me get this straight: You're saying that by taking NR, I'm boosting NAD+ by making the conventional mitochondrial glucose pathway more productive. But, implicitly, MCT oil doesn't really help me because it isn't capable (at least in my case) of producing much more NAD+ than my moderately dysfunctional glucose pathway. (That would make sense, as no one ever said that ketogenic diet was conducive to maximum performance, only maximum endurance.) However, in cases of cancer or dementia, the glucose pathway is so utterly broken that MCT is actually much more productive of NAD+, which is why it has made headlines in such diseases.
 

I know this has been discussed before, but what's the state-of-the-art tolerable upper intake estimate of NR? Can I just take 100 mg any time I notice brain fog onset?

 

@sthira: You might want to create a thread on meniscus issues. This is an important topic that affects some other users I know, and you obviously have a lot of history to contribute.

Edited by resveratrol_guy, 01 November 2015 - 12:33 PM.

[Bryan_S]

 

We all remember our basic biology and our aerobic metabolism is tied to NAD. Below shows the decline in NAD with age.

Source Correlation between NAD+ levels and Age in (A) Males (B) Females.. From: Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue http://www.ncbi.nlm....rt=imagesdocsum

 

I'm looking for the right graphs and cant find the one on mitochondrial decline with age.  If Astor is monitoring this thread he may have that information at hand. I believe it correlates well with the NAD decline data. 

 

This data also closely correlates with the decline. Source "Meta-analysis of the age-associated decline in maximal aerobic capacity in men: relation to training status"

 

There is also the a reduction of mitochondrial membrane potential correlating with age. All this data fits hand in hand with increasing rates of cancer and age related disease. 

 

In answer to you question on maximum intake that hasn't been published yet. However looking at Nicotinamide which has been well studied generally speaking up to 3 grams per day is well tolerated. The "Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention" study used 500mg's twice per day.

 

Being that this is a NR experience thread we should likely take this discussion to another thread.

Edited by Bryan_S, 01 November 2015 - 05:07 PM.

[resveratrol_guy]

Wow! All I can say is that those graphs look horrible. I didn't realize that the decline starts so early relative to generalized senescence, which suggests that NAD+ decline gives rise to other diseases (as though that's news). I'm now more motivated to continue NR on a regular basis. If 3 g/d nicotinamide is an informative limit, then I don't think I have much to worry about, as that would be prohibitively expensive. Anyway, thanks for this data set.

[sthira]

Would intravenous NAD be more effective for those with low levels? Is there a specific blood test for NAD deficiencies? Can we take NAD blood tests before and after consuming Niagen to check how NAD levels are affected? Someone must be doing this, right? Is there data for it? For example, 20-50 year old endurance athletes are tested for NAD levels before and after taking 1g daily Niagen? How difficult and expensive would such a test be for companies already profiting from charging customers high fees for the Niagen product they're already claiming has X effect on athletes?

[BigLabRat]

.... The result seems to have been alertness to the point of pain, which only subsided with choline ingestion. I might be misinterpreting the event, but it was unprecedented in my memory, so I thought to report it.

 

Can someone enlighten me as to why choline should have an effect? It is mentioned 2 or 3 times wrt NR, but with no real discussion.
 

[sthira]

Would intravenous NAD be more effective for those with low levels? Is there a specific blood test for NAD deficiencies? Can we take NAD blood tests before and after consuming Niagen to check how NAD levels are affected? Someone must be doing this, right? Is there data for it? For example, 20-50 year old endurance athletes are tested for NAD levels before and after taking 1g daily Niagen? How difficult and expensive would such a test be for companies already profiting from charging customers high fees for the Niagen product they're already claiming has X effect on athletes?

Here's a Reddit thread asking the same obvious questions I just asked more than 500 days ago. https://m.reddit.com...level_question/

So I'm assuming those tests were probably done (NAD blood tests before and after Niagen consumption) and they probably found nothing, and now simply aren't telling us they found no rises in NAD levels so we'll just stay in the dark and keep buying their product on faith that it does something positive? If they'd found a rise in NAD by consuming Niagen you can bet your boots they'd be wildly advertising it, right?

[Bryan_S]

So I'm assuming those tests were probably done (NAD blood tests before and after Niagen consumption) and they probably found nothing, and now simply aren't telling us they found no rises in NAD levels so we'll just stay in the dark and keep buying their product on faith that it does something positive? If they'd found a rise in NAD by consuming Niagen you can bet your boots they'd be wildly advertising it, right?

 

 

ChromaDex is playing this for all its worth and the results were posted not long ago. Results from First Human Clinical Study Demonstrate ChromaDex's NIAGEN® Nicotinamide Riboside Effectively Increases the Co-enzyme NAD+ and is Safe

 

Many intravenous and oral NAD and NADH studies have been done and they generate positive cellular results but have you looked at their relative per gram prices? Plus these more complicated molecules are reduced to simpler NAD precursors to cross the cell membrane anyway so whats the point of spending more money to achieve the same thing. We covered this on the Updates thread not long ago.

 

One point we didn't cover in those posts is NR is a Sirtuin activator. (SIRT1, SIRT3)

 

So when it comes to questions and finding answers your in the right crowd.

[BigLabRat]

 

Would intravenous NAD be more effective for those with low levels? Is there a specific blood test for NAD deficiencies? Can we take NAD blood tests before and after consuming Niagen to check how NAD levels are affected? Someone must be doing this, right? Is there data for it? For example, 20-50 year old endurance athletes are tested for NAD levels before and after taking 1g daily Niagen? How difficult and expensive would such a test be for companies already profiting from charging customers high fees for the Niagen product they're already claiming has X effect on athletes?

Here's a Reddit thread asking the same obvious questions I just asked more than 500 days ago. https://m.reddit.com...level_question/

So I'm assuming those tests were probably done (NAD blood tests before and after Niagen consumption) and they probably found nothing, and now simply aren't telling us they found no rises in NAD levels so we'll just stay in the dark and keep buying their product on faith that it does something positive? If they'd found a rise in NAD by consuming Niagen you can bet your boots they'd be wildly advertising it, right?

 

 

"So I'm assuming those test were probably done...and they probably found nothing..."

 

That's a rather silly assumption.

 

This issue hasn't been around long enough for all those trials on humans to have been approved, completed, and analyzed. Don't forget that commercial manufacture of this supplement only began in 2013.

 

However, they HAVE found a rise in NAD, in humans, from consuming Niagen, and it HAS been "wildly publicized." And extensively discussed on this forum. I suggest you consult the NR news thread circa August 2015--or Google "Nicotinamide Riboside", "Chromadex," and "study results".

 

Whether these results are preserved in the long term is unproven. But that's not exactly a surprise, since the supplement has only been manufactured for a short period, so long-term studies would require time travel.

 

As to questions you ask, no, there is no blood test for NAD deficiencies that I know of. And it's not entirely clear that blood levels of NAD would tell you what you want to know.

 

How expensive would all those studies be? Very. And they wouldn't do all of the possible things they can think of all at once. They only moved from mice to humans recently.

 

In addition, how much money do you really think these companies are making off this? Only a tiny tiny fraction of the population have ever heard of NR, and only a fraction of that tiny tiny fraction are actually buying it.

 

Chromadex produces more than just NR. But the whole company's market capitalization value is only about $150 million, and it most recent quarterly net profit was MINUS $315,000. (Which is up from last year's result for the same quarter of MINUS $1.6 million.) If NR proves out, Chromadex could become immensely profitable, but right now they are still swimming in red ink.

 

All the hype about NR may or may not prove out--or it may remain confused and controversial (think resveratrol). But there certainly aren't studies that have been suppressed.

[sthira]

Thanks for all that information. It's fascinating, and I didn't mean to come across as conspiratorial, although it looks like I sure did :-(

I guess I'm wondering if there are no NAD blood tests checking levels, then how were those graphs Bryan just posted that indicate NAD levels created?

[resveratrol_guy]

 

.... The result seems to have been alertness to the point of pain, which only subsided with choline ingestion. I might be misinterpreting the event, but it was unprecedented in my memory, so I thought to report it.

 

Can someone enlighten me as to why choline should have an effect? It is mentioned 2 or 3 times wrt NR, but with no real discussion.

 

I'm wondering the same. I just downed an egg on a hunch that I was severely choline defficient based on the feel of the symptoms, and it worked rapidly. It seems to me that so much NR put my brain in acetylcholine overdrive, depleting choline. But maybe there's more to it than that. And BTW I didn't know that others had mentioned this. Interesting.

[Bryan_S]

Thanks for all that information. It's fascinating, and I didn't mean to come across as conspiratorial, although it looks like I sure did :-(

I guess I'm wondering if there are no NAD blood tests checking levels, then how were those graphs Bryan just posted that indicate NAD levels created?

I always post the studies as above when we need a reference. Use the bold text below to find the methods and procedures within the studies.

 

Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue

See Measurement of Intracellular NAD+ levels

They did the analysis themselves and outline the procedure.

 

Meta-analysis of the age-associated decline in maximal aerobic capacity in men: relation to training status

See METHODS

It appears they collated oxygen consumption data from an array of studies. Also see REFERENCES

 

This question of NAD testing has come up before and this is what I found. I contacted Genova Diagnostics Clinical Laboratory back in March and they said they could put together the proper testing. https://www.gdx.net/ I've posted this twice since and I think maybe it was expensive or to involved because I don't think anyone was willing to foot the bill or organize all the steps. For those interested I suggest electing someone with a Biochemistry background who needs to decide what biomarkers need to be tested based on what Genova can test for and they can decide how the samples must be collected and preserved for shipment. Genova Diagnostics said they could walk one of us through the steps.

 

Hope that helps.

Edited by Bryan_S, 02 November 2015 - 12:21 AM.

[BigLabRat]

Thanks for all that information. It's fascinating, and I didn't mean to come across as conspiratorial, although it looks like I sure did :-(

I guess I'm wondering if there are no NAD blood tests checking levels, then how were those graphs Bryan just posted that indicate NAD levels created?

 

Sorry if I came off over-snarky.

 

The full Chromadex-sponsored study isn't available yet (just summaries), so we don't know their exact methodology they are using. But their summary at Clinical Trials said they would be monitoring Niagen metabolites as well as NAD from whole blood.

 

That latter sounds like a "blood test"--hey, it's blood,innit?--but unless they have come up with a major innovation, its actually a tissue sample which is broken down by enzymes on a microtitration plate. So it isn't like a normal blood test, where you're measuring the concentration of something circulating in the plasma. It actually measures the amount of NAD in the red blood cells. It's rather complex, and subject to all manner of problems (especially in how the samples are handled temperature-wise).

 

It's not like, for example, a blood sugar test, or a cholesterol test, which test what's in circulation. (For a long time, they assumed there was zero NAD in the extracellular environment. They were wrong, as it turns out; but most of it is in fact, inside the cells.)

 

So, there are tests, but they are either inferential (various metabolites) or complex (tissue breakdown and analysis). And as various papers show, the effects of different precursors (i.e. NA, NMN, NR, Nam) on NAD content of cells differs between different tissues of the body. (And in many cases, NA is more impressive than NR.) The effect of NR on NAD content of Red Blood Cells is being measured...but is that indicative of what NR does to the body in general? Not clear. Suggestive, but not conclusive. 

 

And in one study back in 2007, they concluded that, in patients with clinical pellagra from niacin deficiencies, the NAD content of Red Blood Cells was NOT depressed (as would be expected). Not clear what that proves, but it certainly shows things aren't straightforward. And our analytics in this area are in their infancy. 

[ironfistx]

do we have to worry about anything getting out of whack if we take NR for a while and then stop?  Or if people in their youth take it?

[BigLabRat]

Good question. I can only offer a half-assed answer: Nobody knows.

 

I suspect that NR works like most vitamins or intermediary metabolites, in which case things will readjust when supplementation ceases.

 

The main problem seems to come with hormones, or hormone analogues, where the downregulation is severe and often partially irreversible. But there is nothing so far that I know of to suggest a hormone-like response. So I'm not really concerned.

 

But others may have different thoughts on the subject, and I'd be interested to hear them.

[Bryan_S]

do we have to worry about anything getting out of whack if we take NR for a while and then stop?  Or if people in their youth take it?

 

NAD is deeply tied to your circadian rhythms. So boosting levels near bedtime might fool your body into thinking its time to get productive. Your NAD levels naturally fall near bedtime anyway and levels increase in preparation for the day ahead before waking. So your day to day life is intimately tied to this metabolite and its best to complement rather than oppose your natural rhythm.

 

I'm not your typical user, I take NR by day but I also use the sedative effects of Nicotinamide at night. 

 

As a side note I've used Nicotinamide Riboside on back to back marathon work days to stay alert, although I wouldn't recommend this over sleep because its a cheat. We all know you can not cheat sleep and at some point you have to pay the piper and bed down for some solid sleep. 

 

If you're asking about addiction, lets just say you were born addicted to this molecule called NAD and we need it for our day to day existence. Being an older NR user I've gotten used to being more alert, like I once was when I was younger. I've discontinued NR's use on occasion and to be honest I like the way I feel now and don't like going back to the way I was.

 

Being young is great, from that perspective preventing the cellular degeneration of aging would seem to be the goal. If the research proves out in humans as it has in animal studies you may be able to delay some aspects of aging but you need to be a realist. For one, don't get wrapped up in all the $$ marketing hype surrounding the David Sinclair studies. I mean specifically pump pieces written by people trying to get you to buy their brand of Niagen. At this point no one can make you any guarantees until the human research is proved out and for now you'll need to weigh the animal studies yourself.

 

Here is the rub, being young your not as likely to feel the NAD boosting benefits because you don't carry around the deficits like us old farts. So where is the motivation to maintain a longterm NR regiment if your already feeling good? Believe me I've been down this road with my son. Your going to have to be convinced of the benefits by reading study after study where the benefits of boosting NAD offset some cellular defect of aging or disease. We have a thread listing those studies but it will not be an overnight read. The NAD boosting benefits have been verified, and the metabolism involved is so basic its been conserved across all mammalian species. So its nearly impossible to consider it doesn't apply to us but that's my opinion. 

Edited by Bryan_S, 04 November 2015 - 09:21 AM.

[BigLabRat]

Bryan, can I ask what your NR and Nam intake levels are at present?

 

I noticed a significant bump in energy when I first started NR, but it soon subsided. And discontinuing for 2 weeks didn't seem to have a perceptible effect. (Nor was there a perceptible rebound when I started up again.)

 

Niacinamide, on the other hand, still has a powerful effect on my sleep (even at just 500 mg). And Niacinamide + Glycine is the best sleeping potion I've ever discovered. (I've been vegetarian for decades, so a Glycine deficiency is not improbable.)

[Bryan_S]

Bryan, can I ask what your NR and Nam intake levels are at present?

 

I noticed a significant bump in energy when I first started NR, but it soon subsided. And discontinuing for 2 weeks didn't seem to have a perceptible effect. (Nor was there a perceptible rebound when I started up again.)

 

Niacinamide, on the other hand, still has a powerful effect on my sleep (even at just 500 mg). And Niacinamide + Glycine is the best sleeping potion I've ever discovered. (I've been vegetarian for decades, so a Glycine deficiency is not improbable.)

 

With NR I use 1,000 mg per day spread evenly across the daylight hours. I take 2,000 mg of Nicotinamide at the end of the day before bed and can get to sleep usually within 10 minutes.

 

You bring up an important point about Glycine and its funny it doesn't have this effect on me in the morning but your point is well taken.

[Rocket]

 

Bryan, can I ask what your NR and Nam intake levels are at present?

 

I noticed a significant bump in energy when I first started NR, but it soon subsided. And discontinuing for 2 weeks didn't seem to have a perceptible effect. (Nor was there a perceptible rebound when I started up again.)

 

Niacinamide, on the other hand, still has a powerful effect on my sleep (even at just 500 mg). And Niacinamide + Glycine is the best sleeping potion I've ever discovered. (I've been vegetarian for decades, so a Glycine deficiency is not improbable.)

 

With NR I use 1,000 mg per day spread evenly across the daylight hours. I take 2,000 mg of Nicotinamide at the end of the day before bed and can get to sleep usually within 10 minutes.

 

You bring up an important point about Glycine and its funny it doesn't have this effect on me in the morning but your point is well taken.

 

 

NR sure does sound like a total bust.  From my own experience to what people here write, no one has gotten even a little of the effect that Sinclair got in mice when injecting NMN.  Meanwhile the manufacturer keeps ripping everyone off and people keep buying another useless supplement.  Seems like another useless overpriced supp.

[BigLabRat]

 

You bring up an important point about Glycine and its funny it doesn't have this effect on me in the morning but your point is well taken.

 

 

I've never tried it in the morning--I've feared it would have me snoring on the floor. But that might not be the case at all: Glycine has both sedating and stimulating properties in the brain. Maybe it's photoperiod sensitive? I'll have to try the experiment some time. (It rather surprises me that Glycine hasn't received more attention around here--the stuff has all manner of beneficial effects, and it's cheap as dirt.)

 

But I'm close to hijacking this thread, so I should get off Glycine and back to NR.

 

I'm not so sure that Rocket is correct that NR is a total bust. If one reads this whole thread, reports have been all over the place. And I'm not entirely sure that we ought to notice a massive subjective effect at the kinds of doses being used.

 

I personally noticed the effects more from Niacin, but Niacin has obvious effects that have nothing to do with NAD, so it may be at least partly psychological. I sometimes toy with the idea of doing all three--Niacin, Nicotinamide, and NR--at different times of day. Since the Niacin pathway to NAD is largely separate from the Nam/NR pathway, it seems it might give an extra boost. But I worry about giving my liver that much of a processing load...

 

At any rate, I'm not sure NR is a bust. The science still looks promising. But I'm also not sure what the emerging consensus is, either. Or if we even have an emerging consensus!
 

[Rocket]

 

 

You bring up an important point about Glycine and its funny it doesn't have this effect on me in the morning but your point is well taken.

 

 

I've never tried it in the morning--I've feared it would have me snoring on the floor. But that might not be the case at all: Glycine has both sedating and stimulating properties in the brain. Maybe it's photoperiod sensitive? I'll have to try the experiment some time. (It rather surprises me that Glycine hasn't received more attention around here--the stuff has all manner of beneficial effects, and it's cheap as dirt.)

 

But I'm close to hijacking this thread, so I should get off Glycine and back to NR.

 

I'm not so sure that Rocket is correct that NR is a total bust. If one reads this whole thread, reports have been all over the place. And I'm not entirely sure that we ought to notice a massive subjective effect at the kinds of doses being used.

 

I personally noticed the effects more from Niacin, but Niacin has obvious effects that have nothing to do with NAD, so it may be at least partly psychological. I sometimes toy with the idea of doing all three--Niacin, Nicotinamide, and NR--at different times of day. Since the Niacin pathway to NAD is largely separate from the Nam/NR pathway, it seems it might give an extra boost. But I worry about giving my liver that much of a processing load...

 

At any rate, I'm not sure NR is a bust. The science still looks promising. But I'm also not sure what the emerging consensus is, either. Or if we even have an emerging consensus!
 

 

 

I guess you will have to wait and see the results of Sinclair's human trials with NMN as a comparison.  But I have seen nothing in this thread and from my own use for months that this supplement duplicates Sinclair's mice experiments.  My own experiments with GH releasers had REAL results.  Same with SARMS and muscle development. Other peptides had real and noticeable effects.  NR, literally, nothing even at very high doses for a long period of time.  Again, everyone will have to wait for the Sinclair human trials to end to have a baseline for comparison, but certainly no one here has reversed muscle aging as in the Sinclair experiment.

Edited by Rocket, 05 November 2015 - 06:05 PM.

[Bryan_S]

I arrived here from a inflammatory standpoint but its not a cure all as we can see from one members torn knee meniscus report. We are all seeking validation that the money we spent is worth the long term expense. I think peoples dissatisfaction stems from all the over sensationalized interpretations of Sinclair's work. Sinclair himself is also something of a showman so public expectations are naturally a little inflated.

 

Since I have orthopedic problems from a skydiving accident I'm one of the lost soles looking for a miracle. I'm going to have to live with the inflammation from those impairments the rest of my life.

 

So in the real-world my low-grade inflammation will be compounded by normal inflammatory aging, its not pretty but its in the cards for me.

 

What are my choices? (NSAIDs) are out because they eventually cause cardiac problems. Many of the other anti-inflammatory's also cause other problems from longterm use. Then there are the B3 findings that have intrigued researchers for 40-years. Talk about a long term data set to reflect on. When patients report arthritis and other joint problems improving on a B3 regiments you would think Doctors would praise and prescribe the stuff but that hasn't been the case.

 

Slowly research has leaked that they may be on the underlying trail of the inflammatory response and B3 starts to come into focus again from its past studies. Now mind you we're talking about a compound in the patent free zone and followup capital incentives for study are slim. But we're talking about something that has positive side effects instead of negative ones.

 

Hum . . . let me think about the fact that chronic joint issues will need continuous longterm treatment. Then a sideline revelation appears concerning A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention and in this treatment you need to maintain a daily B3 regiment or the protection goes away. Hum . . . Why . . . well that hasn't been explained just yet but is likely because the most critical DNA error checking happens at times of cell division and because these error checking enzymes are NAD consumers and you never know when a stem cell division will happen and when it does you need an adequate NAD pool to do the job when the need arises. So just from an arthritis and cancer prevention standpoint daily NAD boosting makes sense. 

 

We haven't even touched on the protective Spinal, Cerebral or Cardiac Ischemia situations which can touch our lives as we age or the hearing protection for that matter.

 

You have to understand some of us are only looking to blunt the overall inflammatory response without doing harm to the rest of our bodies. So if I'm going to take something systemically for the rest of my life why not consider something that gives me these other benefits. 

 

To this end researchers like Professor Anthony Sauve at Cornell are leading the pack and giving us tangible evidence of how to restore the bodies natural anti-inflammatory mechanisms. He found Fasting produced favorable effects via SIRT3 and NR also activated this and worked well, he's in the thick of it uncovering all the mechanisms involved. So we could go on about all the animal studies and other human clinical trials but there is real un-sensationalized research going on but its being overshadowed by the showman trying to outcompete the others for recognition/funding to find aspects of these pathways to capitalize.

 

It hasn't made me a day younger but I feel a whole lot better than I did. Its also not an exercise mimetic, you still need to get regular exercise to see the oxygen consumption and muscle benefits because sitting on the couch reading this thread isn't going to provide that. I also feel I need to say that 125 or 250 mg per day while still better than nothing, won't carry you thru the entire day but that's my opinion.

Edited by Bryan_S, 05 November 2015 - 09:28 PM.