I've been looking at all of the many, many approaches that have been tried in order to increase NAD+. Niaicin, Niacinamide, NR, NMN are a few. The reasons why NAD+ is important are too numerous to list. If you need just one reason, NAD+ is how the energy we bring in (food) becomes energy that our cells can use for all the many things our cells need to do. It's a large signaling molecule, which simply means that the cell that NAD+ is inside of takes all of its cues from the state of the NAD+. When we're young and healthy, the NAD+ tells the cell to go all-out. As we age, we lose a very large % of our NAD+.
During my search for the product with the best result, I stumbled upon a company that's doing things a little differently. In short, rather than supply more precursor material (there's never been any proof that the reduction of NAD+ as we age is the result of a lack of precursor material), Nuchido Labs has developed a supplement (actually a supplement cocktail) that provides support for the cellular "machinery" that recycles damaged NAD+. It also makes our NAD+ last longer by reducing the errors and inflammation that it has to deal with.
The reason that I'm potentially very interested in this approach? They have the results of one study in which they saw a 242% increase in NAD+ compared to about a 40-60% increase from the best NAD+ precursor product. Now it was a very small study (2 people) but they have just finished collecting all "clinical samples for a 24-person placebo-controlled double-blinded cross-over study. Male and female participants aged between 20-80 consumed Nuchido TIME+ and placebo capsules for 4-weeks at a time, with a 4-week washout period in between. Detailed lab analysis is underway including NAD+ levels, NAD+ metabolite levels and downstream effects of high NAD+ levels."
So, if you want to wait before doing anything, then wait for it. But if you don't want to wait, you can buy it now. Or try to guess their recipe. Because, another thing they're doing differently is, instead of finding a molecule that they can patent and make a lot of money on, they're using existing, well-known and understood "safe" supplements in a specific ratio. They freely provide a list of these ingredients, but not their ratio. These ingredients are all easy to find and inexpensive. How much would guessing the right ratio matter? Maybe not much, maybe a lot, which might make it worth paying their price of about $55/month.
So, if you're almost always broke like I am, you can get all of the ingredients and try different ratios. Or save up for the real deal. They claim that many people see results in 1-2 weeks, so I might get a bottle and see.
Video intro to Nuchido's unique approach to increasing NAD+ : youtu.be/6NEA0hOT4yk
Mercola and Conlon are saying, "NAMPT is a rate limiting enzyme for NAD production" (the diagram indicates more of a recycling loop). Following the arrows Nicotinamide is in front of NAMPT with a direct link to inhibiting Sirtuins (bunt end means inhibits). Both NR and NMN are behind NAMPT with no direct link to Sirtuins.
I step back to saying, NICOTINAMIDE inhibits Sirtuins. This product has NICOTINAMIDE in it.
I feel the increase of Sirtuins is the true benefit behind increasing NAD.
Looks like the relationships are complex. Hard to predict the ultimate result all of this:
"Nicotinamidase is an enzyme that cleaves nicotinamide making nicotinic acid. Since nicotinamide is the primary starting material for NAD synthesis [12], cleavage of nicotinamide may decrease tissue NAD levels. In addition, nicotinamide is an inhibitor of sirtuins [4]. Cleavage of nicotinamide, to nicotinic acid, may activate sirtuins. NAD is synthesized by nicotinamide phosphoribosyl transferase and NMN adenyl transferase. NMN is nicotinamide mononucleotide."
Also added this comment to your post that you link to
See my old response on this below. You're looking at the Salvage pathway diagram that comes after de novo biosynthesis, which applies to pretty much all forms of niacin when ingested orally since they all get broken down to niacinamide. It's the salvage pathway that turns them all into NAD+ over and over in our tissues and past the BBB through nicotinamide molecules.
Thanks for the link. I'm putting together an email to Dr Conlon, asking if she has any advice for PWP. I'll be glad to include any questions or issues you or anyone else here would like me to raise. I'm going to give it a month of thought before I decide if I should jump in for a 2 month test.
Interesting read, but I always take as a grain of salt (as a little truth) if read on a site trying to sell something. It maybe true that regardless of the original dietary source (NAM, NR, NMN or Tryptophan), NAD is going to be recycled from nicotinamide (NAM) and the bulk of used NAD is going to be recycled, I still don't think you should take high amounts of NAM which are going to inhibit Sirtuins (if NAM present in a high enough quantity). I agree it a good idea to promote Sirtuins.
There are plenty of other scientific resources you can look up including others mentioned under the post, and as I've stated earlier that's just a random site that explains rather well for most laymen to read. I agree a high dosage tends to provoke side effects and may magnify subclinical deficiencies in other enzyme co-factors including methyl donor shortage, and that site states pretty much the same about using any B3 compounds.
Again, the main supply of NAD for tissues and the brain will be recycled nicotinamide through the salvage pathway, regardless of the original form of B3.
So is the big investment NR then NMN really marketing or are they scientifically better than just enduring the flush with direct niacin supplementation? I concluded that NR was my best option and I sure wish I took notes to remember why! I believe it is how it has less impact on decreasing methylation and is somehow better in the gut. ?? Then, there’s NADH. Why isn’t it being used much anymore?
The Auburn study used slow release Niacin. No flush. I use time released.
I use time released because that is as close as I can get to slow release. I don't actually mind the flush. I'm thinking time released may provide an optimal dose of niacin to the cells for a longer period of time. That is just my guess.
Also, the NA binds to GPR109A, which is supposed to lower inflammation, which was the whole purpose of the Auburn study.
Sometimes I am stupid. I have been calling this the Auburn study forever!
Raymond Chong1,2*†,Chandramohan Wakade 2,3,4,5 *†,Marissa Seamon2,3,5,
Banabihari Giri2,5,John Morgan 2,4 and Sharad Purohit 2,6
1Department of Interdisciplinary Health Sciences, Augusta University, Augusta, GA, United States, 2Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, United States, 3Department of Neuroscience and Regenerative Medicine,
Augusta University, Augusta, GA, United States, 4Department of Neurology, Augusta University, Augusta, GA, United States, 5Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United States, 6Department of
Undergraduate Health Professions, Augusta University, Augusta, GA, United State
No one is perfect, Bolt. You are not stupid, on the contrary you write like a very intelligent man. Is there anyone who hasn't been confused for one reason or another?
The authors conclude that pretreatment with 325 mg of aspirin before administration of niacin can reduce symptoms such as flushing and tingling which may preclude niacin's use. Increasing the dosage to 650 mg does not provide additional benefit.
The salvage pathway degrades as we get older so the NAD+ turnover goes down for a given amount of precursors, but using high-dose nicotinamide is subject to immediate rate-limiting feedback inhibition for NAD+ production. People pay big money for NR and NMN because they theoretically immediately boost the NAD+ production/storage made available for the rest of the body for relatively higher abundance, bypassing the decline in the expression of the rate-limiting enzyme NAMPT that converts NAM to NMN that comes with aging. While this may be beneficial for boosting the sluggish NAD+ pool, I don't think there's one single superior precursor because they all work/benefit through different pathways, including ATP needed for energy. NA has its place for G-protein coupled receptors, and so do other precursors including the de novo pathway involving tryptophan. Just as there's no best food, there's no single best precursor and when you try to force a singular pathway consistently, you just might hurt the balance or end up causing dyshomeostasis if not careful, such as in methylation pool or other enzymatic cofactors/minerals. I have tried NR but personally have not noticed any tangible benefits to justify the extra cost, and you're much better off boosting NAD+ through consistent exercise, intermittent fasting, better diet, while utilizing all precursors through foods and different forms to optimize all pathways and ultimately avoiding deficiencies.
The NAD+ actually steal electrons and proton from hydrogen from molecules such as glucose and make them available to mitochondria through NADH that end up producing ATP through the Krebs cycle's electron transport chains, so bypassing any step with an intermediary molecule such as NADH (can't replace NAD+' fundamentally important biological role) might initially seem to help in certain mitochondrial dysfunctions but the benefit could only be transient with the perturbed process/ratio, which is probably why it's not used because no tangible long-term benefits were proven. Besides, studies reveal the following, so pushing NADH higher may result in delicate repercussions because the ratio feedback may upset energy production through dynamic regulation.
"Although the exact mechanism of NAD+ decline remains unclear, it is likely that NAD+ levels are regulated by the rates of NAD+ synthesis, and NAD+ consumption. Our data suggest that it is primarily NAD+ that decreases with age to drive this ratio down, since NADH levels do not appear to be significantly changed across age groups. Additionally, there may be other causes of NAD+ decline, including a metabolic shift that does not favor higher NAD+/NADH ratio."
"Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD(+), total NAD contents, and NAD(+)/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.
“while utilizing all precursors through foods and different forms to optimize all pathways and ultimately avoiding deficiencies.”
So maybe my idea of rotating forms wasn’t so off. 🤓 I started with niacin (from Seeking Health) then invested in NMN (Do Not Age) and now I just started NR. I was going back and forth between a few days niacin, few days NMN. I wonder if doing say, 30 days of one then switching would be better?
Your knowledge always inspires me to keep learning!
Yes, use all precursors, and I personally rotate pretty often and depending on other supplements and multivitamin formulations I take. At least initially for most people, it's probably worth experimenting for a stretch to see how you react. I think NA flush is interesting and kind of fun, but I quit when I don't flush anymore, and it tends to cause severe dry eye and blurry vision if I keep up so I primarily use it to help detox combined with rebounding/exercising and sauna, and only take it while fasting (after dinner, etc) because it seriously shoots up my blood sugar otherwise (NA causes diabetes in some people). While using any of the precursors (NR being more potent), improve the main salvage pathway recycling of NAD+ by using dried organic parsley (12x higher apigenin than fresh parsley). The apigenin will lower CD38 to boost NAD+. Other compounds that are generally well known to lower inflammation such as curcumin are also useful since inflammation eats up NAD+.For example, to my late breakfast (more like lunch), I added some quercetin powder(don't forget it's fat-soluble), 1tsp dried organic parsley, a partial 1/4tsp of NR packet, black pepper (piperine), added some blueberries (flavonoids) and had some matcha for EGCG. Weird combo but tasted fine!
Just to give some context regarding PD, I in my modest research have followed this line of Nad + / Nadh with little results for three years with all forms of B3. I mean ... the b3 in all forms is good and I recommend it to anyone who takes C / L and helps a lot to solve the lack of nad + plus many other advantages, but this is not decisive for stop the progression. What I have understood and am still experiencing is that the nicotinic acid form B3 (called niacin here) is much more potent when used to stimulate autophagy and here a door opens that I hope will lead me out of the labyrinth, but it is too early to talk about it. I wrote about it in my last reply to the post on autophagy, where among other things there are mentioned two niacin-derived drugs patented by an Italian pharmaceutical company then bought by Pfizer and marketed under another name (practically b3 niacin slightly modified,), which give the same benefits as niacin, are sold with a prescription and give less flushing.
Perhaps autophagy is the bazooka we need to punch the progression of the disease.
PS.For those who love associations, mannitol and trehalose also cause autophagia, maybe.
Certainly, autophagy is important because the presence of senescent cells (secrets CD38) will promote NAD+ decline. I think people tend to respond differently to different forms of niacin with differing methylation requirements and nutritional bases, so it's worth experimenting and moreover avoid B3 deficiency and boosting NAD+ as much as possible through various means, including exercise. NA is a good candidate based on the Augusta study but a brand new study just came out showing the benefits of NR as well.
I never understood why B3 NR costs so much, or maybe yes.
However I agree with most of what you say, I would not throw that dose of NR from 0 down in the stomach. One thing I have learned in my experience is the gradualness of using B3 and using it with all the other vitamins and minerals for good. balancing reasons you mentioned. Being well fed in various ways, low in fat, Mediterranean diet, lots of vegetables. is the best I know, added a little gymnastics,
IMHO everything NR does the NA does it better. No one who is so fed will suffer from under methilathion, keep in mind that these vitamins are present in food with everything else.
Gio, when you supplement a super dosage of niacin that's unnatural (and in the competition of other B's), you're going to dump methyl donors and will risk raising homocysteine among other problems leading to liver/organ damage. This can't be balanced through a normal diet, especially for people who have genetic SNPs that require more menthyl donors, such as choline which many tend to be deficient. This is why I've been saying people should look into supplementing TMG for methylation support unless they know they're overmethylated. The reason NR costs so much is because it has been proven at least initially it boosts NAD+ much more efficiently than other B3 forms with relatively no side effects... until many people eventually start experiencing problems at sustained high dosage as can be seen on product reviews. On top of that, if your salvage pathway isn't working well for recycling NAD+ in your tissues and brain (even NA becomes NAM for transport/recycling to the brain), you're simply going to waste all that expensive NAD+ down the toilet because the NAMPT enzyme degrades with aging. This is why Dr. Conlon developed the OP product that maximizes the salvage pathway that's critical for constant NAD+ availability by all our cells.
Yes, when you're playing with a high dosage of anything, you're risking gymnastics and must be careful of potential injury, and I"m sure this is why even you have to take breaks from NA from time to time.
emh! ... no, the synthetic form of niacin is called OLBETAM @ Acimipox and its side effects are listed in its box that are the same as B3 niacin if not more. My homocysteine is normal as well as cholesterol as per blood tests. I take breaks because it is my protocol ( based on b3NA) which does not aim to reconstruct the nad + even if it does, but to induce autophagia as per the post I talked about before and I do not use high doses which I do not recommend. Then there would be other little things about NAM which is the form in which all other forms of B3 are transformed, but I will not be annoyed with the pharmacinetics of b3 nr nam etcetra that no one knows well in vivo. You are definitely right when you say we are all different, this is just my experience.my-personaltrainer.it/farma...
Yes, we're all definitely different and I'm glad to hear that your homocysteine level is normal with around 250mg NA dosage? Niacin definitely helps fight cholesterol, which is why many people try the high dose and are even now prescribed for people who can't tolerate Statin. Unfortunately, I can't tolerate even 100mg of NA for too long before I start experiencing problems even with TMG, so I definitely have to be more careful. I tend to be sensitive and experience side effects relatively easily, sort of like a canary in the mine.
I'm going to look into it some more, but my current understanding is that, while it does inhibit sirtuins initially, it goes on to promote them.
Adding (from the interview notes):
She uses a “systems pharmacology” approach to work with the complexity of human biology. Systems pharmacology has three main principles that differ from conventional pharmaceutical discovery, Dr. Conlon says.
“Human biology is really complex and there is a lot going on and it is very robust. It’s built with redundancies in order to withstand an impact generally, and Systems Pharmacology doesn’t ignore that. It actually looks at every single gene, every single pathway, every single protein, every single feedback, feedforward, inhibition; everything that is going on and recognizes that it is a big, extremely complex and intertwined network.”
“It’s never ever scientifically plausible to take a single target/magic bullet approach. Try to put your finger on one tiny little piece of the massively complex puzzle that is our biology. It’s just never going to work."
“You’ve got to take a multi-targeted approach and look at the best combinations of targets within all of that complexity. The goal is to understand how you can affect each one; improve and promote these pathways, while limiting or blocking others, so that everything that was overwhelmed works better than before.”
Nuchido looked at NAD+ through that lens. They wanted to repair and support the ways our bodies' cells retain, repair, and increase their NAD. Other, more problematic behaviors, needed to be suppressed or even completely blocked. Dr. Conlon and her team of scientists and scientific advisors– several who are giants in the field of biogerontology–identified the right combination of targets that needed to be supported or blocked in order to restore cellular NAD+ levels back to youthful norms, leading to the development of a breakthrough NAD+ booster called Nuchido TIME+.
The TIME+ booster restores and improves the cell’s ability to make and especially recycle its own NAD+, makes cells more efficient, stops cells from wasting NAD+, and reboots the efficiency of your salvage pathway. It does this by expanding the problem to include all of the relevant sub-systems and solving their problems, rather than answering one question which often turns out to be insufficient.
You guys got me going and spending all morning researching. Here is what I came up with concerning nicotinamide inhibiting sirtuins and is what someone else mentioned too. You can google this study. It all gets confusing, like you want to inhibit CD38 yet you don't want to completely inhibit it as it is necessary for other things. It is all about balance...or I should say a balancing act.
Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells
I'm leaning towards subscribing for a couple of months. If I do I'll definitely keep everyone up to date. The more I listen to Dr Conlon the more I'm impressed. Listen to more of her interviews and I think you'll agree. youtu.be/_RjmnIbKfZs Many of us have complained in the past about how big pharma is the only way to get funding for research and they won't fund without a patent, but here's a company that is using well tested and "safe" ingredients that are not patented and at a fairly reasonable price. And they seem to be doing the necessary research as well!
Will however pass on the product but will upgrade my quercetin supplement to a more bioavailable form that uses the Sophora Japonica extract, which contains the compounds quercetin, rutin and troxrutin. The key compound here is quercetin.
This enzyme [NAMPT] is critical to the production of NAD+ but declines with age. These compounds [quercetin, rutin and troxrutin] are proven to increase NAMPT enzyme levels and improve NAD+ production.
Also need to put Alpha Lipoic Acid back in the mix
She mentioned that the green tea is in the form EGCG. I decided not to do EGCG but I don’t remember why. (Oops). So I use Matcha powder in the AM and L Theanine in the PM.
Thank you for the Quercitin info. ! I added one to my cart. This is what I have. I have only been using it a couple days a week. Maybe I’m being too cautious and should use it daily?
Will use her insights to put together a NAD program for my spouse.
But I have decided that I will try Nuchido Time Plus for myself. Do not have PD but I am approaching 70yrs. So if it boost NAD spectacularly I should know
Please report back. Keen to learn more. I’m on Quicksilver NAD+ (NMN) as of two weeks ago. Seen research favouring NR (Tru Niagen) so planning to swap - but this other product might be better.
I hope it is better, because I am using Tru Niagen 300mg. 3 pills a day but with no tangible effects from an energy point of view. This does not mean that doesn't work. A member of this community has been using it for some time with benefit. The truth is that we are all different.
Yes, True Niagen didn't do much for my husband, but NA does! I believe because of the flushing effect, they don't promote it. Yet, it's this flushing that suggests it's working and accomplishing its purpose: ENERGY!
I agree that Dr. Conlon is brilliant and the company is great to work with. My husband was on the products for over 3 months. However his routine physical revealed extremely high liver enzymes. When he stopped the product he was retested and his numbers went back to normal. We were able to return the unused three month supply and a complete refund was made. Just want you to be aware of this possibility.
Looking at the ingredients, it's probably the EGCG/green tea leaf extract. It's also possible that he was severely depleted with methyl donors, and if that's the case TMG supplementation could help.
This is the best interview of Dr Conlon that I've been able to find. Absolutely FULL of very pertanant information! Whether you know nothing about NAD+ or you think that you understand everything about NAD+, you need to watch this:
Learnt a lot! I see why you would want to go this route. I may even relent and try the product. Hopefully she has the right balance in there, given her academic background.
I've heard enough and have decided not to wait. I'm buying 3 months' worth. If I get just a little more energy and/or less brain fog, it'll be well worth it. My dX was 13 years ago and I've managed to stay fairly active with exercise, but my meds are becoming less reliable so I have to do more. It's a little bit of a gamble, but it seems like it's based on fairly solid science. It's too bad that it's so difficult (probably impossible) to get NAD levels tested by a lab; it means that any results that I get will be highly subjective. One more thing: the DAVE10 promo code does, in fact, give you 10% off!
Jas, I highly recommend that you test your homocysteine before and after trying the supplement for a period. Also, consider adding 250mg TMG with the product for methylation support.
I've been taking 750 mg of TMG twice a week and 250 mg of NA daily for the past 2 weeks. I'll probably continue that until the Time+ order arrives. I'll take your advice and have my homocysteine tested. I am sending an email asking some specific questions, and I'll ask about TMG in their product.
I did my homework too! ☺️ Excellent interview. I highly recommend it!
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