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NAD+ supplement reverses vascular decline in aging mice

anciendaze

Senior Member
Messages
1,841
This article is so closely related to problems that affect me I'm almost tempted to post this in a different forum. It is about an experimental study in mice, not humans, and nowhere mentions ME/CFS. I will also caution that the doses given mice appear to be much higher than in NAD+ supplements for humans. Here's the announcement from the Perelman School. Here's a link to the paper in Cell.

There are already NAD+ supplements for people though at this point I'm not sure how these relate to the exact form used in research. In biochemistry details matter, and there is no question that bioavailability of some forms taken orally is quite low.

NAD+ has previously turned up in research on nematodes and exit from dauer diapause.
 

junkcrap50

Senior Member
Messages
1,322
Here's a recent thread about NAD+ with discussion.

I think NAD+ has huge potential - for CFS patients, older individuals, and people with chronic diseases. It has a big role in inflammation and energy.

In researching NAD+, I saved a lot of links and sent them to my parents and my doctor so they can learn about it. I posted it in the thread linked above. I'll post it here too.

------------------------------------------------------------------------------------------------------------------------

Thread on Phoenix Rising
(where I first learned about IV NAD+. Pretty short thread.)
http://forums.phoenixrising.me/inde...ical-mitochondrial-genetic-repair-poll.57797/
--The full NAD+ infusion protocol is 7-12 days of 1500mg 8 hour infusions everyday. Each infusion is $1,000-$1,500. This is said to replenish deficient levels, and nasal supplementation can then be continued as maintenance.
--South African doctor came up with an "Energy Value" based on pyruvate and lactate labs to determine your NAD+ levels and your NAD Energy Defeciency (NED) sickness. If your "Energy Value" below 100 indicate a need for therapeutic NAD+.
http://www.lunaliving.org/pdf/nad_therapy_e-book.pdf
--One user on PR (Learner1) says that he takes NAD+ via IV but at smaller doses. Says it gives him energy for a day or two.
--He found a sublingal source of real NAD+, which enabled him to sky for 5 hours.
http://liasresearch.com/
http://liasresearch.com/lias-otc.html
--Intranasal NAD+ is available but supposedly sticky and unpleasant.
Podcast about IV NAD+
Good background and primer on it - much better than next link. Interviews patient who cured his CFS, Ph.D who researches NAD+, and MD who runs NAD Infusion center. Can listen to audio or read trasncript. Worth reading whole thing. Skim the comments too.
Audio: https://bengreenfieldfitness.com/podcast/anti-aging-podcasts/what-is-nad/
Transcript: https://bengreenfieldfitness.com/transcripts/transcript-what-is-nad/
--"A lot of the enthusiasm about resveratrol is the fact that it was theoretically driving sirtuin activity. What’s interesting is that sirtuins are like a factory, like any enzyme, they won’t function unless they have, if you like, the raw material for that factory to work on, and NAD is that raw material."
--NAD works at the epigentic level.
--"Another OTC supplement to raise NAD+ is nicotinamide. It can be recycled through to NAD. The negative thing with having too much nicotinamide, as opposed to the other types of NAD precursor [NR and NMN] that I’ve mentioned, is that nicotinamide is a byproduct. Now, you’ve heard we’ve talked about CD38, we’ve talked about sirtuins, and talked about the PARPS. So CD38, the immune modulators, the Sirts, the epigenetic modulators, and PARPS, the DNA repair enzymes. Now all of those three, when they use NAD, they will actually generate nicotinamide as a byproduct. As the levels start to go up in the cell, the nicotinamide starts to inhibit those enzymes, the CD38s, the sirtuins, the PARPs. And so too much nicotinamide, unfortunately, can stop the very reactions that you want to have acting. So, we would probably suggest that getting it from some of the other sources, the nicotinamide riboside, NMN, or nicotinic acid would be better."
--"You can find nicotinamide riboside as a supplement, and nicotinamide riboside, like NMN, will be converted through to NAD. In fact, nicotinamide riboside is converted first to NMN, and then through to NAD.... But taking the other two, the NR, the nicotinamide riboside, or the NMN, neither of those will produce nicotinamide until it goes through NAD."
--Q: "How big of a difference is there between intravenous NAD and taking NAD as a supplemnt"
A: "We suffer from lack of NAD because we’re using it up and not replenished in proper levels, and it’s the cause of underlying aging, and other disease processes. So I think that you have to sort of flood the body with NAD to start off with, but then you can supplement, and that’s why we use intravenous. Then you can supplement NAD with a pure source of NAD that we give intranasally that I think is a very good method of continuing to substitute to boost your NAD levels."
--NAD+ levels drop 40% as you age. Another study showed every 20 years, you experience a 50% drop in NAD+. Another study tested people under 45 and over 45 for their NAD levels and they found that 300% increase in the average between the pre- 45 and post-45. Also, another study shows that it seems to exponentially increase after age 60 the loss of NAD.
--Can measure NAD levels in blood, but hard to get the lab to do it right. Rapidly degrades after blood draw.
--"Even the MTHFR gene has improved with NAD+."
--From the comments on the audio page link: “In the suprachiasmatic nucleus, biological rhythms are maintained by a central clock of around 20,000 pacemaker neurons.¹ These neurons can degenerate with age and oxidative stress. NAMPT/NAD drives the circadian clock feedback cycle through SIRT1 and Clock:BMAL1². As the NAD levels oscillate over the circadian cycle the activity of SIRT1 oscillates linking the metabolic state of the cell through an epigenetic mechanism to the circadian clock.¹”
Short Scientific Explanation & Background:
http://www.life-enhancement.com/magazine/article/2947-its-a-nad-nad-nad-nad-world
http://www.life-enhancement.com/magazine/article/2986-its-a-nad-nad-nad-nad-world-part-ii
http://www.life-enhancement.com/magazine/article/676-can-nad-help-extend-human-lifespan

NAD+ in Press:
https://blogs.scientificamerican.com/guest-blog/beyond-resveratrol-the-anti-aging-nad-fad/
http://www.dailymail.co.uk/health/article-4370092/Is-pink-pill-elixir-youth.html
https://www.vice.com/en_us/article/bn3vmq/nad-plus-brain-reboot-infusion-injection

Important Papers on NAD+ and aging:
Declining NAD+ Induces a Pseudohypoxic State [my emphsis] Disrupting Nuclear-Mitochondrial Communication during Aging, which we show is reversable (Pseudohypoxic state has been used to describe the pathology of CFS/ME, like a form of sepsis)
https://hms.harvard.edu/news/genetics/new-reversible-cause-aging-12-19-13
Full paper & abstract: http://www.cell.com/abstract/S0092-8674(13)01521-3

NAD Key in Autoimmune Disease: delays disease onset and reverses disease progression

https://hms.harvard.edu/news/new-discovery-regulating-autoimmune-diseases
Full paper and abstract: https://www.nature.com/articles/ncomms6101
"Here we show that administration of NAD+ protects against EAE and reverses disease progression by regulating CD4+ T-cell differentiation and apoptosis through a novel signalling pathway and by promoting myelin and axonal regeneration."

NAD+ Is a Food Component That Promotes Exit from Dauer Diapause in Caenorhabditis elegans

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167208
Note: Naviaux called CFS/ME a "dauer" state and said our metabolimics and disease most closely resembled the dauer state in C. elegans. He's used this same model and dauer state for our disease.
Discussion: http://forums.phoenixrising.me/inde...that-promotes-exit-from-dauer-diapause.57363/

Other NAD+ Papers and Research:
NAD+ and NADH in cellular functions and cell death
NAD+ and NADH in brain functions, brain diseases, and brain aging
NAD+/NADH and NADP+/NADPH in cell ular functions and cell death: regulation and biological consequences.

https://static1.squarespace.com/static/53580835e4b0c3ad7382ddb6/t/5384b2b3e4b0b1911ba23a44/1401205427488/J) NAD+.pdf

Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment.
https://www.ncbi.nlm.nih.gov/pubmed/25678560

Prevention of Traumatic Brain Injury-Induced Neuron Death by Intranasal Delivery of Nicotinamide Adenine Dinucleotide
http://online.liebertpub.com/doi/pdf/10.1089/neu.2011.2228

NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NRNeed to use ATP to convert NR to NAD+
http://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30670-8

Nicotinamide Mononucleotide, a Key NAD+ Intermediate, Treats the Pathophysiology of Diet- and Age-Induced Diabetes in Mice. Cell Metabolism.
https://www.decodedscience.org/nmn-nicotinamide-mononucleotide-lowers-blood-glucose-in-mice/3616

"Clocks" in the NAD World: NAD as a metabolic oscillator for the regulation of circadian rhythem, metabolism, and aging.
http://europepmc.org/abstract/med/19897060

Pharmacological Effects of Exogenous NAD on Mitochondrial Bioenergetics, DNA Repair, and Apoptosis
http://molpharm.aspetjournals.org/content/molpharm/early/2011/09/14/mol.111.073916.full.pdf

Differences Between NAD+ Metabolites Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR):
Niagen offers NR and that's what has been done in human studies showing increase in NAD+. It's also a product that came out first. NMN appears to be better, but there's only a few products of it out there and there isn't a human study showing its effectiveness. TokyoU & WashU are starting a human trial in 2018 to be done in 2020. Links below is from a site that sells NMN supplements, but has some good graphs and data from the research. The site may have more pages that show more info too.
http://alivebynature.com/nmn-or-nr-whats-the-best-nad-booster-3/
http://alivebynature.com/about-niagen/
http://alivebynature.com/does-nr-break-down-to-nam-before-nad/
http://alivebynature.com/in-nmn-the-best-way-to-improve-your-healthspan/
http://alivebynature.com/nicotinamide-riboside-optimum-dosage/

Interesting Evidence:
Total and complete normalization of QEEG scan by NAD+. Look at before and after pictures. Same type of scan I had for neurobiofeedback (they even mention Dr. Jay Gunkelman who read my scan). A lot more effective than neurobiofeedback ever was.
https://emerald-neuro-recover.com/brain-scan

"NeuroRecover ™ has been shown on SPECT brain scans performed at the Dr. Daniel Amen Clinics, in images taken before and after treatment, to promptly bring about significant improvement in function in the drug-damaged brain." I'm emailing and waiting to hear if they have pictures/evidence/a case study of this claim.
http://chwbonline.com/medical-services/neurorecover/

Compounding Pharmacies that Sell It

https://supplementpolice.com/nad/#comment-21937
Archway Apothecary in Louisiana (also do a nasal spray & oral NAD+)
Anazoa Phamacy in Tampa
https://www.alternet.org/drugs/does...iracle-cure-addiction-and-disease-really-work
Hayden Pharmacy
https://www.reddit.com/r/StackAdvice/comments/5pq00p/where_to_get_iv_nad_solution/
College Pharmacy
Comment saying a "full protocol" costs $1,000 from College Pharmacy and having a doctor friend prescribe it.

NAD+ Infusion Clinics Pages:
Springfield Wellness started/brought NAD in/to the US. Longest running clinc providing NAD and have developed the protocols.
http://www.springfieldwellnesscenter.com/
https://custommedicine.com.au/nad-nicotinamide-adenine-dinucleotide/
https://innovativemedicine.com/closer-look-nad-brain-restoration-therapy/
https://www.ivforlife.com/nad-fountain-youth-2/
http://chwbonline.com/medical-services/neurorecover/

Conference on NAD+ Therapy:
https://www.nadsummit2018.com/
http://www.brplusnadsummit.com/about-our-summit/
(From the podcast interview) http://www.brplusnadsummit.com/ross-grant-phd/
(From next NAD+ email and blog, Anti-agingFirewall.com) http://www.brplusnadsummit.com/james-paul-watson-m-d/

Videos / Testimonials
Parkinsons and NAD+

Alzheimer's and NAD+

NADH (not NAD+) and Parkinsons (There have been previous, older studies of NADH improving Parkinsons. This video is pretty extraordinary.)
 

junkcrap50

Senior Member
Messages
1,322
Another information dump.

If you can handle deep scientific literature, then these links is all you need to read on NAD+.

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Very good blog that has a HUGE amount of VERY in-depth research on antiaging science: http://www.anti-agingfirewalls.com/. I mean the depth, detail, and complexity this blogger/scientist covers is remarkable and overwhelming. He has very good articles on all kinds of things, so it's worth browsing the rest of it looking at the article titles. But he goes on a 5 Part review of research into NAD+ that I will link and try to summarize below. Make sure to read the comments at the end/bottom of each article/blog entry.

About the Site/Author:
The author, Vince Guiliano Ph.D.He's currently 88 years old and started the blog when he was 79. He has a PhD in applied physics from Harvard. His first blog post explains what he's does 30-60 hours per week of longevity/anti-aging research. His bio is at the bottom of any blogs writen by him (can't link directly to it). A different bio is here:
http://www.vincegiuliano.name/VGBIObiotech2011.htm

He also has a co-blogger, James P. Watson MD that's contributed a lot to the NAD+ articles. He's spoken at an AMMG meetings and has one talk on youtube. His bio is at the bottom of each blog he writes, but also found here:
http://www.anti-agingfirewalls.com/author/james-watson/

Link to picture of NAD+ pathways/metabolism:
The NAD+ metablism and the different forms of it can be very confusing. So below are some pictures of good metabolish pathways. Part 1 of the blog series has a glossary of all the terms.
http://alivebynature.com/june/wp-content/uploads/NAD-metabolism-in-humans.jpg
https://www.researchgate.net/figure...thways-The-reactions-marked-with_fig8_6470310

Slideshow Presentation (Condensed Overview)
Author gave a talk that is basically a condensed summary of his 5 part review. He also links to his slides. At the bottom of the article he lists the 5 parts of his NAD+ review.
http://www.anti-agingfirewalls.com/2018/01/16/tales-nad-presentation-coming/
(Direct Link to Slides:www.anti-agingfirewalls.com/__oneclick_uploads/2018/01/Giuliano-Lecture-on-NAD2-4-18.pptx)

Notable quotes / bullet points from blog entry and slides
:
"Finally, I comment on the possible reason why IV infusions of NAD may be beneficial when levels of NAD+ are so depleted that oral supplements may not be capable of overcoming the effects of a deleterious positive feedback cycle."
-- NAD+ is used in both consuming and non-consuming processes.
Slide 16: Note how Nictoninamide (NCA) blocks Sirtuins
--Vital role in circadian rhythem (genes: PER2, CLOCK)
"If your circadian rhythms and body clocks are off, NAD+ and Sirtuin enzyme levels may be too low, resulting in body circadian clocks not work well."
"nicotinamide inhibits Sirtuins"
"With aging there is not enough NAD+ to satify the multiple needs for it. Its usages in the body are triggered and rationed, with negative conseques across the body."
"Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging."
"Because there is much positive feedback among these Cycles if something goes wrong, and there are many many opportunities for this to happen,, the body may not be able to restore healthy NAD+ and NAD+/ NAD ratios without an extraordinary intervention. I strongly conjecture that IV NAD infusions are now the best and possibly only way to provide such a rebooting intervention."

NAD+ an emerging framework for health and life extension
Part 1: The NAD World
http://www.anti-agingfirewalls.com/...rk-for-life-extension-part-1-the-nad-world-2/
Part 2: Deeper into the NAD Wrold and Hopeful Interventions
http://www.anti-agingfirewalls.com/...per-into-the-nad-world-hopeful-interventions/
Part 3: 30 Major Factors that Control SIRT1 Expression, SIRT1 Activity, and SIRT1-mediated Aging
http://www.anti-agingfirewalls.com/...ging-framework-for-health-and-life-extension/
Part 4: The NQ01 gene, the Warburg effect, SIRT 1 and inflammation, and possible interventions
http://www.anti-agingfirewalls.com/2015/05/01/part-4-of-the-nad-world-the-nq1-gene-the-warburg-effect-sirt-1-and-inflammation-and-possible-interventions/
Part 5: the conflicting roles of NAMPT – inflammation or rescue? Also Part 1 on a new series on inflammation
http://www.anti-agingfirewalls.com/...-also-part-1-on-a-new-series-on-inflammation/
Part 6: How Google is getting into NAD+ businesss, why Google’s strategy will fail, why NR/NMN/NAD+ will not stop aging.
Not yet published

Other Articles that Discuss NAD+:
http://www.anti-agingfirewalls.com/...list-of-things-i-learned-about-aging-in-2013/
http://www.anti-agingfirewalls.com/...lation-nmn-preventing-diabetes-and-longevity/
http://www.anti-agingfirewalls.com/2014/04/14/shedding-new-light-on-circadian-rhythms/
 

wastwater

Senior Member
Messages
1,267
Location
uk
I likely missing GMDS gene that’s involved in NADP+ binding and protein binding not sure if a supplement would help
I’m interested in getting an EEG
Not sure uk nhs would acknowledge QEEG
Deficiency of GMDS Leads to Escape from NK Cell-Mediated Tumor Surveillance Through Modulation of TRAIL Signaling
 
Last edited:

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
A few comments...

- NAD+ can definitely help those of us who have issues making ATP

- NAD+ is not a cure. If you have other issues, they need to be addressed, too.

- NAD+ is not the same as nicotinamide riboside. They are not interchangeable.

- If you start NAD+, ramping up is a good idea to avoid side effects.

- What works for addicts in addiction clinics may not be the same for ME/CFS patients - we have different issues.

- NAD+ does not need to be compounded. There's one from LIAS Research, in Tennessee, that comes in different doses.

- NAD+ is helpful in IV form but expensive

- Watch labelling. There are products that say they're NAD, but they are either some form of niacin or NR, not NAD+.

I've been getting weekly infusions with 150mg NAD+ and taking 50-75mg of sublingual lozenges. My doctors are moving me to 150mg a day.

It has been helping and I could do more. However, I've been slammed with PEM, worse than in months, because I was doing more. More NAD+ and more hydrocortisone did not help. I found 4-5g BCAAs (isoleucine, leucine, saline) pulled me back out of PEM.

The experience highlighted my PDH block, and deficiencies in multiple amino acids, which are consistent with Fluge and Mella's findings, and Chris Armstrong's. So, now I need to solve that to get out of the roller coaster of energy that I've been living.

I'd found nicotinamide riboside was useless to my body, even in high doses.

NAD+ is great, but you need to get a pure version of it, and go slowly, being aware that bit can help unmask other problems. It can also the up your immune system and make one feel sicker in the short run. And while it can help a lot of things, it is not a cure.
 

anciendaze

Senior Member
Messages
1,841
- If you start NAD+, ramping up is a good idea to avoid side effects.
This is general advice for any supplement or medication. Also, try to limit changes to one at a time, so you know which change is causing problems. This takes longer, but it is less likely to fail because of adverse reactions that were not actually caused by the intervention.

Over the years I've found many things that made me feel better for a short time, but made problems worse days later. If you don't trust your memory of how you felt while trying something, keep a journal showing what you were doing and how you felt. In my case, things that made me feel better 3 days after a change have been most helpful. This is not how common human psychology works, and that is one reason there are alcoholics and drug addicts.