74 replies to this topic

[Brian Valerie]

Hi, all!  For my first non- "Introduce Yourself" post, I'd like to suggest the possibility of a 4-5 days on, 2-3 days off cycle for NAD+ precursors, based on the advice in the NMN manufacturer ALIVEBYNATURE website's "Sublingual Bioavailability" article.  I find this at least somewhat credible, since it's not in their business interest to have their customers cycle off of their product at all, which may be why this advice does not appear on the bottle itself!  Since we're barely on the frontiers of the relevant research, I can only hope that the timing of their suggested cycling is based on some empirical evidence.  In recent weeks, I've been cycling 4 days of NMN and NR, then 3 days of sulforaphane, and would much appreciate hearing any other opinions.  Thanks! 

Edited by Brian Valerie, 14 August 2018 - 10:39 PM.

[able]

I've been contemplating this subject myself for many weeks.  I personally seem to get a bit tired or groggy after a week or so of higher doses (over 1,500 mg).

 

I read Turnbuckles thread on manipulating mitochondria with interest, and think the fusion/fission makes a lot of sense, but haven't really tried it as I cant figure out how to fit it in with my fasting and exercise routine.

 

After reading the research last week about stearic acid inducing fusion all by itself, it convinced me to try that, and am waiting on delivery of stearic acid supply from amazon tomorrow.

 

I plan on alternating sublingual NMN for fission, and on off days, stearic acid for fusion.

[XenMan]

Alive by Nature have gone a little bit ‘off script’ promoting NMN as a performance enhancer for the elderly lately. I use their product, but take it once a day in the morning at the moment.

 

There have been some discussions here on NMN cycling, suppression and homeostasis. I would never confess to being the font of all knowledge, but I would draw a few facts to your attention on making your decision on use:

 

As an anti-aging protocol, natural levels of NAD+ decrease as you get older to the point that these low levels increase chances of age related disease. My guess is at around 50, is the beginning of potential problems. You can take NMN daily to increase circulating levels, as the mouse experiments show there is no suppression of natural NAD+ levels with supplementation. Your natural decreasing levels plus what you add from NMN keep circulating NAD+ levels high enough to prevent disease.

 

Possibly from any age, extra NAD+ in your system will make you ‘feel better’, improve physical and mental performance, and even reverse some signs of aging. Nothing works in isolation, and even though circulating levels of NAD+ may be constant with supplementation, its impact on other compounds in your body may change and adapt as you get with many supplements. This is why you may get a noticeable impact when you first take it and a normalisation later. When you were young you had high levels of NAD+, but you still felt 'normal'; this is how your body likes to be.

 

As you may have seen already from testimonies, results vary with NAD+ supplements. This doesn’t mean it doesn’t work, just that as we are all different, results will vary. I have had a few 50+ associates take it and they have felt nothing.

 

There may be other undocumented benefits from cycling, as suggested in another thread on mitochondria fission and fusion (Manipulating Mitochondria), but at this stage there aren’t any published papers I’m aware of with evidence and a mechanism for the benefits of long term cycling.

 

[able]

Alive by Nature have gone a little bit ‘off script’ promoting NMN as a performance enhancer for the elderly lately. I use their product, but take it once a day in the morning at the moment.

 

 

I don't think they are  promoting NMN as a  performance enhancer for the elderly, but more as proof it is actually working, which makes some sense to me.

 

The latest Sinclair mouse study showed huge improvement in endurance for the older mice, but we naturally wonder if it will translate to humans.

 

If they can show that their NMN is yielding similar results for performance in humans, it implies it might be providing  the other benefits  we see in mice.

 

I can say that I have more energy, joints don't hurt, and just feel better, but that doesn't really mean much.

 

If their little contest finds a lot of people that actually document their improvements in racing like this guy that Sinclair tweeted about, it seems a lot stronger to me.

Edited by able, 15 August 2018 - 02:09 AM.

[XenMan]

I don't think they are  promoting NMN as a  performance enhancer for the elderly, but more as proof it is actually working, which makes some sense to me.

 

I received an email regarding ‘body transformation’ and after ‘older athletes’. This is on the site:

 

“…Even more shocking, I have experienced muscle growth that is beyond what I EVER had in my 20’s…”

 

Even the recommendation of taking 4 to 8 times a day is for the extremists. Once a day, everyday will do the LE job with benefits in exercise. Back to my post above, it works as in the experiments and with the mechanism described.

 

There is no harm in higher doses, feeling better or how you use it. The problem is that it could be seen as the single answer, which it definitely isn’t, or you have to feel it to get benefits. We are both in agreement that it works with just different approaches to the use. COQ10, hormone modulation, a good diet and lifestyle is just as important.

 

From a scientific perspective, and personal view, there is a bit of misrepresentation on the site; even though I use their product and would vouch for its effectiveness.  

[Nate-2004]

Both NMN and NR and even NAM show a boost in NAD until the body likely reaches homeostasis, which could take weeks. 

 

Sinclair seems to think this essential molecule has a large effect on why we age because of its possible effects on blood flow among other things. See the latest video of his talk posted elsewhere in this forum. It's a highly informative video for sure.

 

I personally think that for now, cycling it in and out on a monthly basis is probably your best bet for optimizing the benefits of taking it. It's certainly not so good as just solving the problem of why it drops in the first place but it'll do until we have other options. I just bought more NR recently and will be cycling it (with chamomile or apigenin) in  and out with sulforaphane, partly to save costs but also to improve its performance. 

 

As far as NR vs NMN, I think it all comes down to your biology.  I personally notice positive benefits from NR but it could be NMN would not affect me well, I don't know, I'm waiting for better sources and cheaper prices to find out. It could be that the people who have reported ill effects from NR benefit greatly from NMN. Maybe there is some mechanism behind their specific differences in biology. We'll know one day in the future perhaps.

 

A recent Rhonda Patrick video discusses cycling on a deeper level than this and I think it's one of those things that rings true for a whole lot of stuff, from exercise, to fasting, to supplements, even to learning, work and hobbies. Life operates in cycles, rhythm is important not just in music, but in sleep, sex and other functions. We live in an era of abundance where it's possible to just do one thing for way too long, and we end up in dysfunction because of it. Cycles are the way to go man. Our bodies constantly try to achieve some sort of homeostasis, and the stresses we throw at it, depending on how often, can hurt us, or it can help us in a hormetic sort of way. I take modafinil, but I don't take it every day, I take it every 4 days. Why? Because my body will develop a tolerance otherwise.

 

And again, also, it saves money.

Edited by Nate-2004, 15 August 2018 - 05:48 PM.

[Brian Valerie]

Thanks for the thoughtful replies, friends!  To summarize thus far, we have ALIVEBYNATURE's 4-5 day on, 2-3 day off cycle, Able's daily cycle (cycling with stearic acid), Nate's monthly cycle (cycling with sulforaphane), and XenMan's healthy scepticism ("Show us the evidence!") about cycling at all.  To support Nate's monthly protocol, we do have the work of Dellinger, et al, who have demonstrated that NAD+ is raised by its precursors to about 90% for about a month before beginning its drop off to about 40% above baseline.  This is preliminary evidence for the monthly cycle, but obviously not proof of its superiority.  Now, can ANYONE show XenMan (and the rest of us) ANY other scholarly evidence for cycling NMN and/or NR?  Hey, at this point we'll consider ANY evidence we can come up with! 

[XenMan]

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.

Ryan W. Dellinger et al

 

“The 40% increase in NAD+ concentration observed in the NRPT 1X group was sustained at 60 days. The increase in NAD+ levels seen in the NRPT 2X group was sustained at approximately 55% over baseline at 60 days.”

 

“This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD+ levels sustainably.”

 

The believers can't be moved, but when the authors use the word "sustainably" they are not recommending or suggesting cycling.

[Oakman]

There is some overlapping advice from ABN regarding cycling. Here it is recommended to take 2-3 days off/wk (and so 4-5 days taking NMN). The significant point mentioned is that this ideally should NOT be done on rest days, or days with least exercise. This suggests that NMN is best utilized WITH significant exercise, i.e., that it is most useful to boost immediate energy production (makes sense). This split schedule would work great if you exercise 4-5 times a week, but do most people do that? Doubtful. So that leaves a bit of a quandary about how long to take NMN and how long/when to cycle off, if, say you only exercise a couple times a week, say on weekends.

 

Alternatively, ABN has recommended to me to take NMN 6 days, cycle off 1 day while on the 3 month, 1000mg/day test.

 

Perhaps the key point is that everyone might get benefit from an approximate 40/60 split, especially when doing exercise. While older folks, myself included, AND those who can actually do exercise often (for myself that is 3-5 times a week) that an elevated dosing level can help even more before cycling. That's just my opinion, nothing more.

 

Myself, I find that cycling 'feels good", both with NMN and supplements in general.  After taking something for a while, stopping for a few days seems to let the body relax, resume 'normal' operation and get back to some intrinsic level, much like taking a deep breath does, then exhaling and relaxing, before continuing on. Also I find that during that off cycling, the benefits of whatever seem to manifest itself to the fullest, sort of a delayed effect. This is all gut feel stuff, something I've always paid close attention to that over the years.

 

With all cutting edge stuff, and with little scientific study to rely on, no one definitively has the 'right' answers to these question just yet. The fun part is we're all working on finding these answers, one N=1 test at a time!

[Brian Valerie]

Great controversy!  I found it rather disconcerting to suspect that the management of a company (ABN) that was sophisticated enough to manufacture and market molecules of beta-nicotinamide mononucleotide would base the timing of their suggested off-cycling (after 4 days, 5 days, or in the case of athletes in their high-dosage experiment like Oakman, after 6 days) on little more than arbitrary whimsy, so I contacted them this morning and spoke with their Chief Operating Officer, the cordial Monica.  She told me that these cycling suggestions were based not only on general theories of homeostasis, but also on evidence that some elevation of NAD+ is sustained up to 72 hours after the last dose, as in the 4 days on, 3 days off protocol.  So it's really sort of a "compromise cycling protocol" for lack of a better term.  Just thought you'd all like to know!  

[XenMan]

...general theories of homeostasis, but also on evidence that some elevation of NAD+ is sustained up to 72 hours after the last dose...

 

A general idea and an observation by a retailer. I thought you people were better than this.

[able]

Is your argument with the concept of cycling NAD precursors?  

 

 

Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.

Ryan W. Dellinger et al

 

“The 40% increase in NAD+ concentration observed in the NRPT 1X group was sustained at 60 days. The increase in NAD+ levels seen in the NRPT 2X group was sustained at approximately 55% over baseline at 60 days.”

 

“This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD+ levels sustainably.”

 

The believers can't be moved, but when the authors use the word "sustainably" they are not recommending or suggesting cycling.

 

The Elysium  study you quote from is probably the single biggest factor that made me think cycling might be a good idea.

 

They found NAD was 90% at 30 days, and down to 55% at 60 days.

 

It's likely to  be even lower at 90 days.

 

It's also quite likely higher than 100% at 15 days.

 

The line you quote is not useful at all for your argument, imo

 

“This study shows that a repeat dose of NRPT is a safe and effective way to increase NAD+ levels sustainably.”

 

I don't think "SUSTAINABLY" is an accurate description (at least not as you are applying it here)

 

It is dropping, due to homeostasis.  It might sustain an increase of 40% or so, but that is a long ways from where it starts, and from what us older folks need to see to get back to levels we had in youth. 

 

If you can modify the protocol to try and avoid that HUGE drop in effectiveness, what is the problem?

 

If cycling 5 days on and 2 days off does not help to avoid the impact of homeostasis, so what?  You save a few bucks.  I just fail to see what your problem is with the concept, or, with ABN proposing something that would actually lower their sales.

Edited by able, 17 August 2018 - 11:24 PM.

[Oakman]

 

....

 

It is dropping, due to homeostasis.  It might sustain an increase of 40% or so, but that is a long ways from where it starts, and from what us older folks need to see to get back to levels we had in youth. 

 

If you can modify the protocol to try and avoid that HUGE drop in effectiveness, what is the problem?

 

If cycling 5 days on and 2 days off does not help to avoid the impact of homeostasis, so what?  You save a few bucks.  I just fail to see what your problem is with the concept, or, with ABN proposing something that would actually lower their sales.

 

 

Exactly. There is no definitive answer yet. But we all make doseage/cycling decisions and feel the result, if any. Everyone seems focused on finding the best recipe for real world NAD+ release. 

[stefan_001]

I have used NR about 3.5 year continuously and have not noticed a drop off. I have experimented with dosing and method but never did a washout. Currently taking 250mg oral in the evening (liver health) and 250mg sublingual in the morning. The sublingual works, I have woken up now and then with a slight headache, its gone after sublingual administration.

 

What I do rotate are various ather supplements e.g. fisetin, milk thistle (should help NAD boosting), pterostilbene. Also for a few months using Taurine.

 

What I write now is pure speculation but I would believe Brenner who uses 2 x 250mg per day tests himself regularly. Afterall he is the "test subject" in the Trammel thesis and tested his blood. And as he doesnt talk about need for cycling.

[Kentavr]

You can take NMN daily to increase circulating levels, as the mouse experiments show there is no suppression of natural NAD+ levels with supplementation.

 

I ask you to provide a link to the study + a specific place where this is said. I have not found it yet.

[Harkijn]

There may be many causes for the drop off to 40%. If the body gets used to heightened NAD+ and uses more NAD+ to do more DNA repair, then that's homeostasis too!

[stefan_001]

There may be many causes for the drop off to 40%. If the body gets used to heightened NAD+ and uses more NAD+ to do more DNA repair, then that's homeostasis too!

 

Small comment. The increase from baseline was 90% at 30 days versus 55% at 60 days for the high dose. So the drop off of total NAD+ is actually 19% only.

 

And if it does increase CD38 then who knows if that is good or bad. CD38 seems to slow prostate cancer development for example.

Edited by stefan_001, 19 August 2018 - 11:25 AM.

[able]

There may be many causes for the drop off to 40%. If the body gets used to heightened NAD+ and uses more NAD+ to do more DNA repair, then that's homeostasis too!

 

 

Dr Brenner's NAD+ increase in the liver was 270% at day 1.  So the increase is clearly dropping as time goes by. 

 

I agree, we don't know why it is dropping and if it is a bad sign or not.

 

The natural response is to say homeostasis kicks in and the liver just stops using the NR to convert to NAD+, and it gets wasted.

 

But it could also be the body adapts and is sending more CD38 to the liver, which breaks it down to NAM and sends it out to the rest of the body (according to Liu study).  We don't know if that would be good, bad, or neutral.

 

Or, after some time at elevated levels, more NAD+ escapes from the liver and is used elsewhere.

 

To me, it would seem that getting more NAD+ to tissues beyond the Liver is the main goal, however that is accomplished.

 

I don't think we really have a clue what is going on though.

 

I noticed feeling better if I take a few days off, so am just going with that.  

Edited by able, 19 August 2018 - 02:54 PM.

[Oakman]

^ able, I love your attitude about all this 'controversy'!  With all we know (meaning all researchers know and can communicate to us) about these questions - truly we are in the same pickle we are with so many topics... in a state of constant confusion. Much like life, love, climate, happiness, vegetables and sugar, salt, fat, and cabs... trying to come to the ultimate truth of the matter eludes us. Simply too many variables and constant changes to fully comprehend how best to proceed. Sort of like stone age man staring at fire, knowing how useful and important it is, not able to control or predict exactly what to do with it.

[XenMan]

 

Is your argument with the concept of cycling NAD precursors?  

 

There is no argument.

 

High dose, low dose, cycle or not; everyone benefits from NMN.

[Michael]

I have used NR about 3.5 year continuously and have not noticed a drop off.

 

Really? You've gone in to a lab sophisticated enough to test whole-blood NR/NMN, NAM, MeNAM, and NAD+ (and, preferably, taken muscle biopsies as well), and determined that you are neither encountering a reduction in NAD+ levels from their peak, nor an excessive buildup of potentially deleterious metabolites? Why didn't you say so sooner? Please post your data, even if it's only an n=1 anecdote.

[stefan_001]

Really? You've gone in to a lab sophisticated enough to test whole-blood NR/NMN, NAM, MeNAM, and NAD+ (and, preferably, taken muscle biopsies as well), and determined that you are neither encountering a reduction in NAD+ levels from their peak, nor an excessive buildup of potentially deleterious metabolites? Why didn't you say so sooner? Please post your data, even if it's only an n=1 anecdote.

 

Michael you know the answer to that. But for me its simple I tracked a number of issues and here some of them. At 45 years old retreating hairline, eyesight deteriorating -0.5 left / right and glaring (had decided to get glasses), need to urinate high (always getting up in night and could not sit out long meetings). At 48,5 years old hairline recovered about 1 cm and still recovering. Eyesight less than -0.5 in test couple months back and glaring very minor (no plans or need for glasses). No need to urinate in the night, no problems during day. All of those issues should have worsened so not only did it get halted they are reversing - and that already for 3.5 years. I think I have reached by now the peak of my homeostatic resistance so yeah REALLY!

Edited by stefan_001, 21 August 2018 - 07:52 PM.

[Nate-2004]

Really? You've gone in to a lab sophisticated enough to test whole-blood NR/NMN, NAM, MeNAM, and NAD+ (and, preferably, taken muscle biopsies as well), and determined that you are neither encountering a reduction in NAD+ levels from their peak, nor an excessive buildup of potentially deleterious metabolites? Why didn't you say so sooner? Please post your data, even if it's only an n=1 anecdote.

 

Michael I don't know where you live but if it's anywhere near Philly, I'm in an NR cycle right now but once I finish I can wash out for a few weeks and get blood work to test this if you know of a place that does it in the area, or even a reliable service online. I'll get a baseline and then I'll cycle it in for a week or two, do it again, then again at 60 or 90 days. Then I will wash out, cycle it back in after 30 to 60 days and then do the same first test after a week or two. Not sure how much that would cost but it can't be more than the NR itself can it? My regular dose is 250mg twice daily (morning and bedtime).  Personally I do notice a fall off at a point, but if I stop for a while and start again the feeling I described (a continuous zing of energy) comes back.

 

I'm 52 hours into my fast right now and it ends around 110-120 and this time around I started with the above dosage, I don't feel even remotely as tired or hungry as I did the last time. My ketones were at 1.7 earlier when I tested.

Edited by Nate-2004, 22 August 2018 - 01:54 AM.

[Phoebus]

Michael I don't know where you live but if it's anywhere near Philly, I'm in an NR cycle right now but once I finish I can wash out for a few weeks and get blood work to test this if you know of a place that does it in the area, or even a reliable service online. I'll get a baseline and then I'll cycle it in for a week or two, do it again, then again at 60 or 90 days. Then I will wash out, cycle it back in after 30 to 60 days and then do the same first test after a week or two. 

 

great idea! love it 

 

hope you do this and post results. 

[Nate-2004]

great idea! love it 

 

hope you do this and post results. 

 

Well, if I knew where and how much to get it done.

[LongLife]

Alive by Nature have gone a little bit ‘off script’ promoting NMN as a performance enhancer for the elderly lately. I use their product, but take it once a day in the morning at the moment.

 

There have been some discussions here on NMN cycling, suppression and homeostasis. I would never confess to being the font of all knowledge, but I would draw a few facts to your attention on making your decision on use:

 

As an anti-aging protocol, natural levels of NAD+ decrease as you get older to the point that these low levels increase chances of age related disease. My guess is at around 50, is the beginning of potential problems. You can take NMN daily to increase circulating levels, as the mouse experiments show there is no suppression of natural NAD+ levels with supplementation. Your natural decreasing levels plus what you add from NMN keep circulating NAD+ levels high enough to prevent disease.

 

Possibly from any age, extra NAD+ in your system will make you ‘feel better’, improve physical and mental performance, and even reverse some signs of aging. Nothing works in isolation, and even though circulating levels of NAD+ may be constant with supplementation, its impact on other compounds in your body may change and adapt as you get with many supplements. This is why you may get a noticeable impact when you first take it and a normalisation later. When you were young you had high levels of NAD+, but you still felt 'normal'; this is how your body likes to be.

 

As you may have seen already from testimonies, results vary with NAD+ supplements. This doesn’t mean it doesn’t work, just that as we are all different, results will vary. I have had a few 50+ associates take it and they have felt nothing.

 

There may be other undocumented benefits from cycling, as suggested in another thread on mitochondria fission and fusion (Manipulating Mitochondria), but at this stage there aren’t any published papers I’m aware of with evidence and a mechanism for the benefits of long term cycling.

XenMan; I have followed the NAD research since 2012. I have been taking NMN daily for only three months as it can not be brought into some countries (ordered and received via Customs) due to regulations agains vitamins and food substitutes. Great is the USA in this respect - freedom. So I get it by chance when relatives travel.

 

Hydrogen sulfide and related substances that increase sulfur in the body from food sources increase NAD levels, acting as an indirect precursor but does not increase NAD levels as high as taking a precursor. I have been taking AliveByNature NMN product and my wife NADH+ by MAAC10. Cycling makes sence. 

NAD levels decrease with age...that is due to the increased presence of an enzyme which consumes NAD.

[LongLife]

I have used NR about 3.5 year continuously and have not noticed a drop off. I have experimented with dosing and method but never did a washout. Currently taking 250mg oral in the evening (liver health) and 250mg sublingual in the morning. The sublingual works, I have woken up now and then with a slight headache, its gone after sublingual administration.

 

What I do rotate are various ather supplements e.g. fisetin, milk thistle (should help NAD boosting), pterostilbene. Also for a few months using Taurine.

 

What I write now is pure speculation but I would believe Brenner who uses 2 x 250mg per day tests himself regularly. Afterall he is the "test subject" in the Trammel thesis and tested his blood. And as he doesnt talk about need for cycling.

stefan_001; you may look at PUBMED for research concerning PQQ + Pterostilbene, as they go habd in hand, also CoQ10. I find that the articles published at SelfHacked on each of these supplements very well documented. I combine PQQ (every other day) with pterostilbene, CoQ10 and fisetine w/ quercetin for mitochondria and DNA health along with NMN. I am going to start cycling these to see what difference I may feel. If you are concernined about liver health and function then try dandy lion root w/ artichoke along with milk thiste seed. That is an effective comb for fatty liver and liver health in general. 

[able]

XenMan; I have followed the NAD research since 2012. I have been taking NMN daily for only three months as it can not be brought into some countries (ordered and received via Customs) due to regulations agains vitamins and food substitutes. Great is the USA in this respect - freedom. So I get it by chance when relatives travel.

 

Hydrogen sulfide and related substances that increase sulfur in the body from food sources increase NAD levels, acting as an indirect precursor but does not increase NAD levels as high as taking a precursor. I have been taking AliveByNature NMN product and my wife NADH+ by MAAC10. Cycling makes sence. 

NAD levels decrease with age...that is due to the increased presence of an enzyme which consumes NAD.

 

 

Why NADH ?

 

As I understood, the benefit is from increasing the NAD+ to NADH ratio.     

 

NADH seems to be the exact opposite of everything we are trying to accomplish with NR or NMN.

 

Do you notice anything from it?  I have read that it affects mood, which might make users think it is beneficial.  But it might be like many drugs  that make you feel good temporarily, and beat the heck out of you long term.

[LongLife]

Why NADH ?

 

As I understood, the benefit is from increasing the NAD+ to NADH ratio.     

 

NADH seems to be the exact opposite of everything we are trying to accomplish with NR or NMN.

 

Do you notice anything from it?  I have read that it affects mood, which might make users think it is beneficial.  But it might be like many drugs  that make you feel good temporarily, and beat the heck out of you long term.

The following is taken from literature on the website for MAAC10 (NADH+ COQ10):

""Our bodies produce energy from the food we eat in a process called cellular respiration. The energy produced is called ATP and the byproducts are water and carbon dioxide. NADH + CoQ10 are required Co-Enzymes of cellular respiration, without which, energy production or life could not exist. As we grow old, both NADH and CoQ10 are slowly diminished, and so does our stamina, energy levels and vitality. Supplemental NADH + CoQ10 can help improve energy levels, boost stamina and endurance, whether you are old, young or a seasoned athlete. 

During the first part of cellular respiration called glycolysis, two molecules of NAD+ are borrowed to store the energy extracted from each molecule glucose (sugar) and stored as NADH. This makes NADH a form of stored-energy that is charged with two high-energy electrons. Later in the process, near the final stages of cellular respiration, known as the electron transport chain, NADH will pass those energy rich electrons to CoQ10. Finally, ATP is produced, which is the energy currency of every living cell.""

I do not know if this is the 'opposite' you make reference to.

I have taken it (NADH+) for two months then I switch to NMN when it finally arrived. [ I have a VERY DIFFICULT time getting any food supplements here.] I now am taking NMN. I did NOT notice any mood changes, nor has my wife, who has been taking the NADH+ CoQ10 for two +months. We are both past our 60's, in good health and active...sometimes overactive. We do notice more energy, better sleep (those two go hand in hand) and hope for the best, meaning that the research benefits get passed on to us as users of NMN / NADH+. 

If I could, I would cycle between NMN & NADH+, NMN one day and NADH+ the next. I hope to do this after Chrismas (2018) when our next supply will arrive. Also I mentioned before that I take a stack of CoQ10, pterostilbene, PQQ, etc. and therefore I cannot comment effectively on the effects of just the NMN or NADH+. Although after six months of using these supplements I have notice a change in my hair color becoming a shade darker. My beard/mustach changed from white to a colored + white arrangement. No new hair growth (80% bald). No hair changes in my wife; she's been using the NADH+ for almost three months.

[Brian Valerie]

One more thought on cycling is that an obvious objection to cycling off of NAD+ precursors or any supplement is that one might be missing out on the beneficial effects for those off-cycle days.  An idea I'd like to offer for those of you who might be reluctant to try cycling for this reason is to maintain your total weekly (or monthly) mg intake, but concentrate it into your on-cycle days.  So instead of 250 mg daily without cycling, you might try upping your dosage to 375 mg daily with cycling, for example.  You wouldn't save any money this way, but it never hurts to have another option!