2266 replies to this topic

[MikeDC]

Interesting, but I don't want to take the risk of stopping Niagen. Low NAD+ does nasty things.

[Nate-2004]

Actually I forgot to mention I stop for 3 days or so after each bottle.

[bluemoon]

Actually I forgot to mention I stop for 3 days or so after each bottle.

 

I think Biotivia recommended a break at some point, maybe after a month, when they started to sell NR, but I haven't seen any other vendor recommend this. 

[Nate-2004]

 

Actually I forgot to mention I stop for 3 days or so after each bottle.

 

I think Biotivia recommended a break at some point, maybe after a month, when they started to sell NR, but I haven't seen any other vendor recommend this. 

 

HPN recommends it right on the bottle. 

 

Also I recently noticed a change in the color for HPN I don't know if they changed the filler or what. It's an even more off white color.

[bluemoon]

 

 

HPN recommends it right on the bottle. 

 

Also I recently noticed a change in the color for HPN I don't know if they changed the filler or what. It's an even more off white color.

 

 

Thanks, I missed that - small print! I'd like to see the science behind that recommendation.

[MikeDC]

I don't think there is any science in stoping Niagen every month for a few days. It was advised as a fear of side effects. As long as you don't take mega doses I don't think one need to take a break. I am afraid of taking a break. What if cancer started during the break?

[Richard McGee]

 

 

 

HPN recommends it right on the bottle. 

 

Also I recently noticed a change in the color for HPN I don't know if they changed the filler or what. It's an even more off white color.

 

 

Thanks, I missed that - small print! I'd like to see the science behind that recommendation.

 

 

"Recent studies have shown that supplementation of NR at pharmacological levels can provide physiological or metabolic benefits by boosting NAD+ levels."(http://onlinelibrary....201600878/full)

 

And what do we know about increased NAD+ levels? Here is one data point:

 

NAD+ and Sirtuins in Aging and Disease:

 

"In addition to these canonical uses of NAD+ and NADH, PARPs transfer ADP-ribose from NAD+ to itself, histones, and other proteins at sites of DNA damage to facilitate repair and maintenance of genomic integrity (Figure 1b). Damaged DNA recruits PARP and activates its poly-ADP-ribosylation activity in situ. Thus, acute DNA damage, for example by ionizing radiation, can trigger a sudden depletion of NAD+due to PARP activation. PARP inhibitors are in clinical trials as anti-cancer agents 10, because they can sensitize tumor cells to apoptotic killing by genotoxic agents through the prevention of DNA repair." [bolding mine]

 

So, the conclusion I draw is this: prevention of DNA repair is a legitimate targeted method of inducing apoptosis of cancer cells. However, you do not want to consistently subvert DNA repair on a long-term basis. This is the opposite of longevity. There are many other more suitable methods of reducing cancer risk. Periodically halting NR to allow biogenesis to reassert itself is a strategy whose benefits far outweigh its risks, while still enjoying the benefits of enhanced NAD+.

 

PGC-1α controls mitochondrial biogenesis and dynamics in lead-induced neurotoxicity

 

In a lead-induced model of neurotoxicity, the following was observed: "Strikingly, the role of PGC1α was found to be equivocal. While a modest increase of PGC1α expression provides a neuroprotective role, dysregulation of expression either by knockdown or overproduction is non-tolerated, leading to neurotoxicity."

 

So, more is not always better. One mouse study concluded that "30 mg NR/kg diet constitutes the optimal concentration to support metabolic health." This would translate to 2.5 mg/kg for humans - or about 250 mg for a 100 kg individual. 

 

Everyone should make their own risk/reward determinations, of course. But for me, if I were to contemplate a long-term NR regimen, I would limit it to 250 mg and incorporate a scheduled break periodically. During this break I would stock up on stearic acid foods in my diet, and possibly add in some PQQ supplementation. (I do use NR periodically, but not long-term.)

Edited by Richard McGee, 06 August 2017 - 10:29 PM.

[MikeDC]

30mg/kg diet. Not body weight. Mice only eat 5g per day. It is a very small dose. About 3mg/kg. For humans it is 150mg-300mg.
If you apply the scaling factor of 12. It is even lower.

[Richard McGee]

30mg/kg diet. Not body weight. Mice only eat 5g per day. It is a very small dose. About 3mg/kg. For humans it is 150mg-300mg.
If you apply the scaling factor of 12. It is even lower.

 

30/12 = 2.5

So, about 2.5 mg/kg NR for humans, after applying the scaling factor. The 150 - 300 mg  range for humans would be in the right range.

[MikeDC]

30mg/kg is the food mice eat. It is not body weight.

[Hebbeh]

The human equivalent dose would be closer to 50 mg/day assuming a mouse weighs 20g and eats 5g/day (figures commonly used).

 

30mg NR per kg food x 5g eaten per day = .03g NR per 1000g food x 5g eaten =

0.03 / 1000 x 5 = 0.00015g NR per day per 20g mouse

 

0.00015g x 1000g / 20g = 0.0075 g NR per kg (mouse) = 7.5 mg per kg mouse

 

7.5 / 12 (scaling from mouse to HED) = 0.625 mg NR per kg human

 

0.625 mg x 75 kg = 47 mg average human 

 

 

 

[Richard McGee]

Not sure where you're going with this. The study I cited specifically says the following: "30 mg NR/kg diet constitutes the optimal concentration to support metabolic health" (in a mouse study). In the cited ratio, kg refers to bodyweight. Don't be confused by the 'diet' reference here; the 'mg NR/kg' is a standardized ratio. It refers to a particular substance versus bodyweight as a ratio for a particular species in an administered diet. This number will be constant regardless of the actual weight of food consumed.

 

 

Overview

The methodology for determining injection volume in rodent studies is dependent on how accurate each injection must be for the overall research design.

For the greatest accuracy in dosing, each individual animal is weighed, and that result is used for the equation: Calculated injection volume (typically measured in "ml") = multiply animal's weight (kg) x dose (mg/kg) and divide by the concentration (mg/ml).

Example:

Mouse: 25g body weight (0.025kg)

Required dose of test substance: 10mg/kg
Concentration of test substance: 1mg/ml

Needed dose: 0.025kg x 10mg/kg = 0.25mg
Needed volume: 0.25mg / 1mg/ml = 0.25ml test substance

xperimental_techniques/calculating_injection_dose_rodent.html

 

 

The dose by factor method applies an exponent for body surface area (0.67), which account for difference in metabolic rate, to convert doses between animals and humans. Thus, HED is determined by the equation:

HED (mg / kg = Animal NOAEL mg/kg) × (Weightanimal [kg]/Weighthuman [kg])(1–0.67)      Eq. (1)

For example, for a newly developed drug molecule, the NOAEL value in rat weighing approximately 150 g is 18 mg/kg. To calculate the starting dose for human studies, use Equation 1.

 

https://www.ncbi.nlm...les/PMC4804402/

 

Edited by Richard McGee, 07 August 2017 - 12:22 AM.

[Hebbeh]

The study explicitly stated

 

either 5, 15, 30, 180, or 900 mg NR per kg diet

 

which plainly means per kg chow eaten not kg mouse weight.  They didn't weigh the mice or measure the daily consumption of food unlike the unrelated reference where they weighed the mice for individual measured injections.  Apples and oranges.  The mice were given standard rations of chow.  Not precisely measured doses calculated individually for each individual mouse.  This is how mouse studies using chow are done.

[Richard McGee]

Mea culpa. You are correct about feed weight in this study.

 

Let's approach this from a different angle.

 

The NOAEL (No adverse affect level) for NR is defined in its GRAS is shown here:

 

http://alivebynature...optimum-dosage/

 

Using the chart here from the  FDA guidelinesfor calculating this to HED of 2880 mg for a 130lb person. With the FDA required 10x safety factor, that would equate to a dose of 288 mg per day for a 130lb human. That is likely the limit on what sellers will recommend, but many people have been taking 500-1,000mg a day with no noticeable side effects.

 

I have to recant my earlier statement - the particular study does indeed refer to diet weight. My apologies. I would however point out that the HED (human effective dose) calculation is based on bodyweight.

 

HED (mg / kg = Animal NOAEL mg/kg) × (Weightanimal [kg]/Weighthuman [kg])(1–0.67) 

Dose is equally related to body weight although it is not the lone factor which influences the scaling for dose calculation. The correction factor (Km) is estimated by dividing the average body weight (kg) of species to its body surface area (m2). For example, the average human body weight is 60 kg, and the body surface area is 1.62 m2. Therefore, the Km factor for human is calculated by dividing 60 by 1.62, which is 37 [Table 1]. The Km factor values of various animal species [Table 1] is used to estimate the HED as:

 

HED (mg / kg) = Animal dose (mg / kg) × (Animal Km / Human Km)  

 

 

https://www.ncbi.nlm...les/PMC4804402/

 

Thus HED does not usually take into account weight of feed. But you are right. If we use standard scaling, the optimum human dose for metabolic correction (implied by this study) may be much lower than the usual (NOAEL) dose.

Edited by Richard McGee, 07 August 2017 - 01:11 AM.

[Phoebus]

probably in this thread somewhere, but can someone point me to info that shows Niagen is clearly better at raising NAD+ levels than regular old B3 nicotinamide?

 

thank you

[Fafner55]

1. “Nicotinamide riboside is uniquely and orally bioavailable in mice and humans” (2016) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062546/ https://brenner.lab.uiowa.edu/sites/brenner.lab.uiowa.edu/files/wysiwyg_uploads/Trammell16c.pdf
2. “Nicotinic acid, nicotinamide and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition” (2008) https://www.ncbi.nlm.nih.gov/pubmed/18429699  

 

1. “A conserved NAD+ binding pocket that regulates protein-protein interactions during aging” (2017)
2. “The NAD+ precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate” (2000) http://www.nature.com/cdd/journal/v7/n3/full/4400658a.html?foxtrotcallback=true
3. “Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair” (2010) https://www.hindawi.com/journals/jna/2010/157591/
4. “Effects of Niacin Restriction on Sirtuin and PARP Responses to Photodamage in Human Skin” (2012) http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042276
5. “Targeting SIRT1 to improve metabolism: all you need is NAD+?” (2012) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616312/
6. “Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition” (2008) 
7. “Niacin or niacinamide supplementation – good or bad idea?” (2010) http://www.anti-agingfirewalls.com/2010/03/30/niacin-or-niacinamide-supplementation-%E2%80%93-good-or-bad-idea/
8. “Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice” (2016) https://www.ncbi.nlm.nih.gov/pubmed/28068222
9.  “Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1” (2002) http://www.jbc.org/content/277/47/45099.full
10. “A conserved NAD+ binding pocket that regulates protein-protein interactions during aging” (2017) 
11. “Nicotinamide's effects on glucose metabolism in subjects at risk for IDDM” (1996) https://www.ncbi.nlm.nih.gov/pubmed/8866571
12. “Using Niacin to Improve Cardiovascular Health” (2007) http://www.lifeexten...7/3/atd/Page-01
13. “Nicotinamide: An Oral Antimicrobial Agent with Activity against Both Mycobacterium tuberculosis and Human Immunodeficiency Virus” (2003) https://academic.oup.com/cid/article/36/4/453/439703/Nicotinamide-An-Oral-Antimicrobial-Agent-with
14. “GENERALLY RECOGNIZED AS SAFE (GRAS) DETERMINATION FOR NIAGEN ™ (NICOTINAMIDE RIBOSIDE CHLORIDE)“ (2015-12) http://www.fda.gov/downloads/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm505226.pdf

 

 

Edited by Fafner55, 10 August 2017 - 01:09 AM.

[Phoebus]

 

MikeDC:

"Niagen could potentially help viruses and bacteria to survive. So better stop it when being treated for infections."

 

what the hell? really?

 

that I did not know.

 

[Heisok]

Phoebus, I have no clue about the viruses and bacteria. It was written by MikeDC, who is an endless promoter of Niagen, so it caught my eye.

[Journey2016]

What do people think to this

http://stemcrave.com/

[PAMPAGUY]

I am a 71 yo male who has posted many times in other forums, but mostly about taking Rapamycin.

 

This is an update on my personal experience with taking NR.  The reason for taking the NR was to increase my energy and stamina.  I received a 6 month supply on August 03, 2017.  Started taking 500 mg daily (250 mg morning, 250 mg evening) + 150 mg Pterostilbene morning.  Have also been taking Rapamycin 6mg. weekly + Metformin SR 1000 mg daily along with, 5mg Crestor, baby aspirin, Lisinopril(hypertensive drug) for 6 months.  I bring this up because there might be a synergy effect with NR.

 

I didn't notice much difference in my energy level or over all feeling until 4 days ago after having taken it for 1 month.  Then all of a sudden, I felt a lot more energy and stamina just in my daily routine.  I really was taken by surprise at the boost in over all good feeling and increased energy.  For someone my age who has noticed the negative aspects of aging for the last 6-7 years this was amazing.  After thinking about it, I have come to the conclusion that my NAD+ has really been increased to the max.  It is the NAD that gives your cells energy.  Now a younger person who's NAD has not been depleted that much, they would probably not notice that much difference.  But for an elderly person who has lost 50% of there NAD due to aging this is a god send.  If this keeps up, I believe I will start running again which I did for many years.

 

I am now on all 3 treatments for aging. (the triad as set out by Dr. Sinclair in his latest video  ).  Reduced Tor signaling with Rapa, (delays cancer, and all other aging diseases) blood glucose control(insulin sensitivity) with Metformin, and NAD+ supplementation with NR.

 

Only time will tell, but at this point in my life, I feel great.

Edited by PAMPAGUY, 02 September 2017 - 11:08 AM.

[albedo]

...  Reduced Tor signaling with Rapa, (delays cancer, and all other aging diseases) blood glucose control(insulin sensitivity) with Metformin, and NAD+ supplementation with NR.

 

Only time will tell, but at this point in my life, I feel great.

 

Happy for you :-) I am sure you will love reading, if not done already, this nice paper discussing precisely the 3 things you are doing for your healthspan (see in particular section 3):

 

Mallikarjun V, Swift J. Therapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New Tricks. EBioMedicine. 2016;14:24-31.

 

If you dare to share: are you following any particular biomarker?

[Gayle63]

I am a 71 yo male who has posted many times in other forums, but mostly about taking Rapamycin.

 

This is an update on my personal experience with taking NR.  The reason for taking the NR was to increase my energy and stamina.  [...]

 

I didn't notice much difference in my energy level or over all feeling until 4 days ago after having taken it for 1 month.  Then all of a sudden, I felt a lot more energy and stamina just in my daily routine. [...]

 

I am now on all 3 treatments for aging. (the triad as set out by Dr. Sinclair in his latest video.  Reduced Tor signaling with Rapa, (delays cancer, and all other aging diseases) blood glucose control(insulin sensitivity) with Metformin, and NAD+ supplementation with NR.

 

Only time will tell, but at this point in my life, I feel great.

That's great to hear! I'm very interested to learn how NR is affecting people in your age range. Very encouraging.

Edited by Michael, 09 September 2017 - 08:39 PM.
trim quote

[whileitravel]

I wish someone in the audience would have asked him why he's not using NR!

[jjnz]

when he says mnm isn't "widely" available does that mean it's not available to buy?

[able]

Its available on Amazon, but about 4x the cost of NR.

 

Also,Fractal Health, the brand that seems best price might be suspect quality.  

 

Anthony Loera (owner of revgenetics, a competitor) had it tested and came back at 5 mg per capsule, instead of the 125 mg they claim on the label.

 

 

Edited by able, 05 September 2017 - 02:31 AM.

[floweryriddle]

Its available on Amazon, but about 4x the cost of NR.

 

Also,Fractal Health, the brand that seems best price might be suspect quality.  

 

Anthony Loera (owner of revgenetics, a competitor) had it tested and came back at 5 mg per capsule, instead of the 125 mg they claim on the label.

 

You can also get it off alibaba from Chinese labs. No idea about quality, but you can - https://www.alibaba....&SearchText=nmn

[PAMPAGUY]

I wish someone in the audience would have asked him why he's not using NR!

[PAMPAGUY]

You are making the same mistake that I did.. Dr. Sinclair is not a pure scientist.. He is also a businessman who uses the science to make money.. There is no money to be made selling NR.. It has become a commodity. NMN trial at Brigham & Womens Hospital in Boston is scheduled to start this month. Funded by private business.. Only around 30 people in first phase to test for safety.. should go quickly.. Second phase will have many more people and take much longer.. Actually NR is a superior precussor to NAD than NMN, but once marketing kicks in people will pay a premium for NMN.

[StanG]

I wish someone in the audience would have asked him why he's not using NR!

 

 

NR gives the same result. He uses NMN because he will make much more money off it! He sold the company he spofe of to SKG for $720mm. 

[Ovidus]

I want to sum up my extremely impressive -and partially surprising- experiences with Nicotinamide Riboside and follow that up with a link to a post, where I compare these experiences with a homemade mix of Nicotinamide + Ribose.

I began by taking one pill of HPN's Niagen, which provides 125 mg of NR. On and off, I went to 2 pills a day to experiment, staying at 2, then going back down to one and playing around to see what would feel best. Overall I had crazy impressive results bordering on a miracle and am summing them up under various headings below.

 

I have been taking NR and then Nicotinamide + Ribose for 2 months now, switching back and forth and trying various combinations.

Mid 40s, male, good health overall, relatively fit, no chronic health issues other than insomnia, for which I will occasionally take Amitryptiline and Seroquel as needed. Only other item I am on is Temlisartan, which I had been on before this experiment and can therefore not attribute any of the below effects to.

 

 

ENERGY
Super energetic and absolutely convinced that I am not talking about placebo here. Somewhat measurable figures such as how many hours a day I was able to stand on my feet during work before needing to sit down, how often I would skip the bus and instead elect to walk, all point to significantly greater energy and very big boost in overall well-being. 

 

ATHLETIC PERFORMANCE

I am an avid weight lifter and find that I am actually able to lift more -as in slightly more and such improvement materializing only upon careful study of the journal, but I am sure it is there. Aerobic performance is also up.

 

DELAYED ONSET MUSCLE SORENESS (DOMS)
Less muscle soreness after workouts; read around the forums and the net and others have experienced this. I find that to be very very good news and think that it points to less overall inflammation (see next post) which is possibly an enormous contribution to the anti-aging effect of this compound. IMO, if you cannot control inflammation, you cannot control or even slow down aging; not that reduced inflammation alone is enough to stop aging, but it is a must, again IMHO.

 

OVERALL INFLAMMATION

I have, what I believe to be two spots in my body that I can use as fairly good indicators of overall inflammation. These are my gums -I experience periodontal issues and gums inflame/re-inflame easily- and my lower back -which gives me problems right away when the overall state of my health and recovery begins to decline. Both have improved tremendously during my run of NR. I know that a lot of things here are very subjective and impossible to present ultra-strong evidence for, but inflammation is one issue that has bothered me all my life. I can therefore very quickly feel any reduction thereof.

SLEEP
This one was a bit strange. For a while NR made it harder to fall asleep, but then I was waking up less beat up than I would have expected, given the little sleep I was getting. This has gone away for some time, and then a month or so into the experiment it has restarted. 

 

SPONTANEOUS RECALL and VERBAL FLUENCY

Enormous impact; unreal experience, absolutely unreal. I am having spontaneous recalls several times a day, sometimes a dozen times every day. I will suddenly remember events, places, people and so on from decades back (in my 40s). The depth and detail of this kind of recall is something absolutely astounding and I have never, absolutely never, experienced anything like it. II am also significantly more verbally fluent and have greater mental endurance. I can read, study and talk for longer periods, and with greater productivity.
However these as well as all other effects pale in comparison to the recall mentioned above. That effect is simply insane. Also a little note; my partner is asking me if I also do not recall negative / sad memories. Interestingly I do not recall anything hurtful. For the most part, I am recalling neutral items, such as a street I used to walk on 20 years ago on my way to school every day. However, these relatively simple memories bring a huge amount of joy, by virtue of their depth and detail. Recalling every cross street I used to walk past on my way, the grandma who was always at the balcony as I passed by and gave me the nod, the narrow passage I used to take as a shortcut and so on is something I had no idea I was capable of pulling up from the depths of my mind. I did not think that under any circumstances I was capable of such recall. It is tantamount to stepping into a time machine; you do not recall memories, but you relive the moment. In fact relive is a word that is thrown around and completely fails to capture the enormity of this experience... Impossible to describe the depth of the feeling really; but you at least get a sense of how impressive I found this aspect of my entire experience. 

 

HUNGER / CALORIC EXPENDITURE

Make what you will of this, but the experiences here have been very interesting. At first NR was appearing to be blunting my hunger. I practice IF, and often do not eat until around 4-5 PM (but continue to eat till I sleep, sometimes as late as midnight). IF became a touch easier at first. However, as I increased the dose to 2 pills and then switched from NR to my home-made mixture, it became harder to go this many hours without food. I want to make sure I do not misrepresent the timeline. Getting hungrier and hungrier occurred over a period of time, and rather gradually. So I cannot completely tie this to my increase of dosage. However, over time it became more and more difficult not to eat.At the moment, I can only wait until late afternoon without food if I have consumed loads of calories the previous day. 
If I have not eaten above normal the previous day, I get hunger pangs and eat a truckload of food a little after noon time. 

I have significantly increased calories -unintentionally, simply because I cannot focus on work unless I satisfy my hunger- and have not gained fat at all. I am fairly certain I have put on muscle and I am equally certain that under ordinary circumstances this additional caloric intake would have turned to fat. I am also feeling warmer and often have to throw away the blanket in the middle of the night, which is consistent with increased Basal Metabolic Rate. 
This effect is very significant by the way and not at all a bump of a hundred calories a day. Maybe the well-read members can tell us if sirtuin activation would cause this. Sirtuins kicking in and doing remodeling /rebuilding/damage repair would cause a need for more calories, but if it can ever be this much I am not sure....


DHT Conversion
This one is very strange and nothing I have come across, as mentioned by anyone else. I was essentially feeling some prostate enlargement and nipple sensitivity, much like you'd feel if you were taking highly androgenic anabolic steroids. This has happened only on high doses of my home-made nicotinamide + ribose mix and subsided -well almost entirely disappeared- when I reduced the dose of nicotinamide + ribose (please see other thread linked). Can someone opine what may be causing this? One idea is simply greater conversion of endogenous testosterone to DHT. Whether plain old nicotinamide can cause this if dosing is sufficiently high, I do not know. Also, if NR would have caused this, had the dose been high enough, or if this can only be caused by my home-made mix of nicotinamide + ribose, I am also unsure of. A slightly more far-fetched possibility is increase in androgen receptor number or sensitivity, while yet another idea is less sex hormone binding globulin (SHBG) which may result in more freely circulating androgens.

 

SIDE EFECTS

How about none, except the falling asleep (and slightly more frequent awakenings at night) and the DHT issue above, which now at a lower dose is just about completely gone.... Now even the sleep, I am hesitant to label as a side effect because I am not suffering the consequences of lack of sleep as a result of the fewer hours I am sleeping. This can thus be simply considered deeper and restful sleep and/or greater energy and consequently just needing less sleep

 

So that's it in sum... I would be most glad to hear any and all opinions, criticism and ideas.

 

 

 

 

Deleted double post.

Edited by APBT, 18 September 2017 - 06:17 PM.